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A new era of doping? Use of peptide and peptide-analog drugs in recreational and professional sport and bodybuilding: a critical review.

Luis F D Coutinho, Lucas F DE Oliveira Neves, Rafael P Camilo

The pursuit of pharmacological enhancement in sport has evolved from the widespread use of anabolic-androgenic steroids (AAS) to novel agents such as peptides and peptide analogues. Marketed as more selective and ostensibly safer alternatives, peptides-including growth hormone secretagogues (e.g., Ipamorelin), growth hormone-releasing hormone analogues (e.g., CJC-1295, Sermorelin), and synthetic fragments (e.g., Frag 176-191, KPV)-are promoted for muscle growth, fat metabolism, recovery, and anti-inflammatory effects. Their pharmacological profiles, including enhanced stability and receptor selectivity, have made them attractive in both medical research and bodybuilding communities. Despite their growing popularity, the clinical evidence supporting peptide use in sport is limited. Most published studies examine therapeutic applications under controlled dosing regimens, not the supraphysiological or combined protocols common in bodybuilding. Emerging data highlight potential risks: cardiovascular strain, insulin resistance, dyslipidemia, and psychiatric instability. The largely unregulated supply chain exacerbates these dangers, as products are often mislabeled or contaminated. Regulatory bodies such as the World Anti-Doping Agency (WADA) have responded by expanding detection technologies, yet analytical challenges remain due to peptides' structural similarity to endogenous hormones and short half-lives. Beyond elite sport, the extent of peptide use in the general population is unknown. Anecdotal reports and widespread promotion on social media suggest growing uptake among recreational gym-goers, including younger individuals, but prevalence studies are lacking. This represents a critical gap in current knowledge. In conclusion, peptides represent a new phase in performance enhancement but remain experimental substances with poorly defined long-term risks. Until longitudinal data clarify their safety and prevalence, peptide use in both competitive and recreational settings should be considered high-risk and ethically problematic.

Growth hormone enhances mitochondria biogenesis and endows mitochondrial thermogenesis in murine adipocytes.

Esha Sadiq, Yinghao Liu, Ni Li +9 more

Growth hormone (GH) can reduce the size of white adipocytes in vivo and in vitro. This catabolic effect was previously believed to be related to the breakdown of stored triglycerides into free fatty acids. However, little is known about its effects on mitochondria in adipose or adipocytes. We thus examined effects of GH on mitochondrial number change and metabolic changes in fat of diet induced obese mice as well as 3T3-L1 adipocytes. We first found in vitro GH increase the density of mitochondria in 3T3-L1 adipocytes. We figured out that GH enhanced the expression of mitochondria biogenesis related genes, such as peroxisome proliferative activated receptor gamma coactivator 1 alpha (Pgc1α), DNA polymerase gamma (Polg) and transcription factor A of mitochondria (Tfam) in vitro and in vivo. To explore the underlying mechanism, we further confirmed that the enhanced expression of these proteins was dependent on the three pathways of GH signaling transduction and that GH enhanced the promoter transactivation of Pgc1α or Polg. We also found that GH increased the cell death-inducing DNA fragmentation factor alpha subunit-like effector A (CIDEA) and uncoupling protein 1 (UCP1) expression by enhancing the promoter transactivation of Cidea. We further elucidated that GH induced UCP1 expression was dependent on CIDEA using CRISPR-Cas9 technique. We therefore conclude that GH has effects on reducing adipocyte size via promoting PGC1α and POLG mediated mitochondrial biogenesis, and also on increasing UCP1 expression via CIDEA. Making adipocytes browning by GH or its analogs may provide a therapeutic strategy for metabolic diseases.

Biomolecules of Adipose Tissue in Atherosclerotic Plaques of Men With Coronary Atherosclerosis.

E V Garbuzova, Ya V Polonskaya, E V Kashtanova +6 more

To study metabolic molecules (adiponectin, adipsin, resistin, glucagon-like peptide-1 (GLP-1), glucagon, secretin) of adipose tissue in atherosclerotic plaques (AP) and their associations with AP instability in men with coronary atherosclerosis.

Effects of gonadotropins, 11-ketotestosterone, and insulin-like growth factor-1 on target gene expression and growth of previtellogenic oocytes from shortfinned eels, Anguilla australis, in vitro.

Anh Tuan Nguyen, Erin L Damsteegt, Jolyn H Z Chia +2 more

Pituitary gonadotropins, metabolic hormones, and sex steroids are known factors affecting the advanced stages of ovarian development in teleost fish. However, the effects of these hormones and of the interactions between them on the growth of previtellogenic ovarian follicles are not known. In order to address this void in understanding, previtellogenic ovarian fragments from eel, Anguilla australis, were incubated in vitro with recombinant Japanese eel follicle-stimulating hormone (rec-Fsh), human chorionic gonadotropin (hCG), or 11-ketotestosterone (11-KT) in the presence or absence of recombinant human insulin-like growth factor-1 (IGF1). The results of long-term in vitro culture (21 days) demonstrated that rec-Fsh and 11-KT, rather than hCG, caused significant increases in the diameter of previtellogenic oocytes. Meanwhile, only 11-KT induced a significant increase in lipid accumulation. Moreover, a greater effect on oocyte growth was observed when IGF1 supplementation was combined with 11-KT rather than with rec-Fsh or hCG. For short-term culture (24 h), treatment with 11-KT in the presence or absence of IGF1 had no significant effects on mRNA levels of target genes (lhr, cyp19, cyp11b, lpl, and ldr) except for upregulation of fshr. There were no significant effects of rec-Fsh on expression of any target gene, whereas hCG downregulated the expression of these genes. There was no evidence for any interaction between the gonadotropins and IGF1 that resulted in growth of previtellogenic oocytes. Taken together, these results suggest that hormones from both the reproductive and the metabolic axes regulate the growth of previtellogenic oocytes in Anguilla australis.

The emerging risk of microplastics and nanoplastics on the microstructure and function of reproductive organs in mammals: A systematic review of preclinical evidence.

Rodolfo C Marcelino, Ronan M Cardoso, Elisa L B C Domingues +3 more

Plastic particles (PP) pollution is a global environmental concern. Although the reproductive toxicity of PP is primarily understood for invertebrates, the evidence for mammals is still fragmented. We used a systematic review framework to investigate the reproductive impact of microplastics and nanoplastics (MNP) on mammals.

Growth hormone replacement may influence the biological action of thyroid hormone on liver and bone tissue.

Nigel Glynn, David J Halsall, Gerard Boran +8 more

Growth hormone (GH) replacement alters the peripheral interconversion of thyroxine (T4) and triiodothyronine (T3). However, little is known about the clinical impact of these alterations. We aimed to compare changes observed in the serum T3:T4 ratio with known biological markers of thyroid hormone action derived from different peripheral tissues.

Effects of exercise training on serum preptin, undercarboxylated osteocalcin and high molecular weight adiponectin in adults with metabolic syndrome.

Gholam Rasul Mohammad Rahimi, Nahid Bijeh, Amir Rashidlamir

What is the central question of this study? Are the advantages of aerobic interval exercise, resistance exercise and concurrent exercise on the metabolic profile mediated in part through preptin and undercarboxylated osteocalcin (ucOCN)? What is the main finding and its importance? Glucose was significantly lowered after concurrent exercise and aerobic interval exercise, but serum preptin and insulin were significantly lowered in all three training groups. By contrast, ucOCN and high molecular weight adiponectin increased significantly in all three training groups. These findings support the possible cross-talk between bone, pancreatic β-cells and energy metabolism in humans and suggest that preptin and ucOCN may potentially serve as markers of exercise-induced improvement of metabolism.

Diphenylbutylpiperidine Antipsychotic Drugs Inhibit Prolactin Receptor Signaling to Reduce Growth of Pancreatic Ductal Adenocarcinoma in Mice.

Prasad Dandawate, Gaurav Kaushik, Chandrayee Ghosh +24 more

Prolactin (PRL) signaling is up-regulated in hormone-responsive cancers. The PRL receptor (PRLR) is a class I cytokine receptor that signals via the Janus kinase (JAK)-signal transducer and activator of transcription and mitogen-activated protein kinase pathways to regulate cell proliferation, migration, stem cell features, and apoptosis. Patients with pancreatic ductal adenocarcinoma (PDAC) have high plasma levels of PRL. We investigated whether PRLR signaling contributes to the growth of pancreatic tumors in mice.

FGF21 Prevents Angiotensin II-Induced Hypertension and Vascular Dysfunction by Activation of ACE2/Angiotensin-(1-7) Axis in Mice.

Xuebo Pan, Yihui Shao, Fan Wu +16 more

Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity. However, the role of FGF21 in hypertension remains elusive. Here we show that FGF21 deficiency significantly exacerbates angiotensin II-induced hypertension and vascular dysfunction, whereas such negative effects are reversed by replenishment of FGF21. Mechanistically, FGF21 acts on adipocytes and renal cells to promote induction of angiotensin-converting enzyme 2 (ACE2), which in turn converts angiotensin II to angiotensin-(1-7), then inhibits hypertension and reverses vascular damage. In addition, ACE2 deficiency strikingly abrogates these beneficial effects of FGF21 in mice, including alleviation of angiotensin II-associated hypertension and vascular damage. Otherwise, pharmaceutical inhibition of angiotensin-(1-7) attenuates the protective effect of FGF21 on angiotensin II-induced vascular dysfunction, but not on hypertension. Thus, FGF21 protects against angiotensin II-induced hypertension and vascular impairment by activation of the ACE2/angiotensin-(1-7) axis via fine-tuning the multi-organ crosstalk between liver, adipose tissue, kidney, and blood vessels.

Structural basis of the signal transduction via transmembrane domain of the human growth hormone receptor.

Eduard V Bocharov, Dmitry M Lesovoy, Olga V Bocharova +5 more

Prior studies of the human growth hormone receptor (GHR) revealed a distinct role of spatial rearrangements of its dimeric transmembrane domain in signal transduction across membrane. Detailed structural information obtained in the present study allowed elucidating the bases of such rearrangement and provided novel insights into receptor functioning.

Age-associated alterations in the levels of cytotoxic lipid molecular species and oxidative stress in the murine thymus are reduced by growth hormone treatment.

Valeria de Mello-Coelho, Roy G Cutler, Allyson Bunbury +3 more

During age-associated thymic involution, thymocytes decrease and lipid-laden cells accumulate. However, if and how aging affects the thymic lipid profile is not well understood, nor is it known if the hormonal milieu modifies this process. Here we demonstrate a correlation between reduced thymocyte numbers and markers of inflammation and oxidative stress with age. Evaluating the lipidomics profile of the whole thymus, between the ages of 4 (young) and 18 months (old), we found increased amounts of triacylglycerides, free cholesterol, cholesterol ester and 4-hydroxynonenal (4-HNE) with age. Moreover, levels of C24:0 and C24:1 sphingomyelins and ceramide C16:0 were elevated in 12-14 month-old (middle-aged) mice while the levels of sulfatide ceramide and ganglioside GD1a increased in the old thymus. Evaluating isolated thymocytes, we found increased levels of cholesterol ester and 4-HNE adducts, as compared to young mice. Next, we treated middle-aged mice with growth hormone (GH), which has been considered a potent immunomodulator. GH reduced thymic levels of TNF-α and 4-HNE and increased the number of thymocytes as well as the thymic levels of dihydroceramide, a ceramide precursor and autophagic stimuli for cell survival. In conclusion, GH treatment attenuated inflammation and age-related increases in oxidative stress and lipotoxicity in the thymus.

A Novel Fc-FGF21 With Improved Resistance to Proteolysis, Increased Affinity Toward β-Klotho, and Enhanced Efficacy in Mice and Cynomolgus Monkeys.

Shanaka Stanislaus, Randy Hecht, Junming Yie +13 more

Fibroblast growth factor (FGF) 21 is a natural hormone that modulates glucose, lipid, and energy metabolism. Previously, we engineered an Fc fusion FGF21 variant with two mutations, Fc-FGF21(RG), to extend the half-life and reduce aggregation and in vivo degradation of FGF21. We now describe a new variant developed to reduce the extreme C-terminal degradation and improve the binding affinity to β-Klotho. We demonstrate, by introducing one additional mutation located at the C terminus of FGF21 (A180E), that the new molecule, Fc-FGF21(RGE), has gained many improved attributes. Compared with Fc-FGF21(RG), Fc-FGF21(RGE) has similar in vitro potency, preserves β-Klotho dependency, and maintains FGF receptor selectivity and cross-species reactivity. In vivo, Fc-FGF21(RGE) showed reduced susceptibility to extreme C-terminal degradation and increased plasma levels of the bioactive intact molecule. The circulating half-life of intact Fc-FGF21(RGE) increased twofold compared with that of Fc-FGF21(RG) in mice and cynomolgus monkeys. Additionally, Fc-FGF21(RGE) exhibited threefold to fivefold enhanced binding affinity to coreceptor β-Klotho across mouse, cynomolgus monkey, and human species. In obese and diabetic mouse and cynomolgus monkey models, Fc-FGF21(RGE) demonstrated greater efficacies to Fc-FGF21(RG), resulting in larger and more sustained improvements in multiple metabolic parameters. No increased immunogenicity was observed with Fc-FGF21(RGE). The superior biophysical, pharmacokinetic, and pharmacodynamic properties, as well as the positive metabolic effects across species, suggest that further clinical development of Fc-FGF21(RGE) as a metabolic therapy for diabetic and/or obese patients may be warranted.

Low-carbohydrate, high-fat diets have sex-specific effects on bone health in rats.

Ayse Zengin, Benedikt Kropp, Yan Chevalier +8 more

Studies in humans suggest that consumption of low-carbohydrate, high-fat diets (LC-HF) could be detrimental for growth and bone health. In young male rats, LC-HF diets negatively affect bone health by impairing the growth hormone/insulin-like growth factor axis (GH/IGF axis), while the effects in female rats remain unknown. Therefore, we investigated whether sex-specific effects of LC-HF diets on bone health exist.

Association study between single nucleotide polymorphisms in leptin and growth traits in Cyprinus carpio var. Jian.

Y Tang, H Li, J Li +2 more

Leptin is a hormone that affects the regulation of body weight, energy expenditure, fat metabolism, food intake, and appetite. In this study, we cloned the jlLEP-A1 and jlLEP-A2 genes in Jian carp (Cyprinus carpio var. Jian) and performed an association analysis between identified polymorphisms and growth traits. Three polymorphisms in exons of jlLEP-A1 (A1-T113C) and jlLEP-A2 (A2-G415A and A2-G427A) were identified, and genotyped by the polymerase chain reaction - restriction fragment length polymorphism method in 263 female and 294 male Jian carp. All three SNPs were missense mutations. Association analysis revealed that the three SNPs were significantly associated with growth traits in male Jian carp. Only SNP A1-T113C was significantly associated with growth traits in female Jian carp. Analysis of diplotypes derived from jlLEP-A2 SNPs revealed an association with growth traits in male but not female Jian carp. These results demonstrate that polymorphisms in the leptin gene are associated with growth traits and may be used for marker-assisted selection programs in Jian carp breeding and production.

Association of a genetic marker at the bovine Janus kinase 2 locus (JAK2/RsaI) with milk production traits of four cattle breeds.

Małgorzata Szewczuk

In addition to the main components of the somatotrophic axis (GH/GHR/IGF-I/IGF-IR), great importance in the control of growth and development is also attached to the Janus kinase 2 (JAK2) pathway. Induced by the GH/GHR complex, JAK2 activates signal transducer and activator of transcription 5 (STAT5), and in consequence, may be involved in the regulation of expression of insulin-like growth factor I (IGF-I) in the mammary gland. Silent mutation (rs110298451) has been identified within exon 20 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A total of 904 individuals of four dairy or dual-purpose breeds (Polish Holstein-Friesian, Montbeliarde, Simmental and Jersey) were genotyped. A genotypic imbalance in the populations was observed. In the case of dual-purpose breeds (Montbeliarde and Simmental), the frequencies of both alleles were almost equal. In contrary, the JAK2G allele was predominant in the Polish Holstein-Friesian breed while JAK2A allele in Jersey. A pronounced relationship between JAK2/RsaI polymorphism and milk production traits was found where, irrespective of breed and lactation order, the GG genotype was significantly associated with higher milk, protein and fat yields, as compared to the AA genotype. Heterozygous individuals were generally characterised by intermediate values of the analysed milk traits. It can be argued that the JAK2 gene polymorphism is a potential marker for milk production traits. However, due to the fact that rs110298451 SNP does not directly affect amino acid sequence, other association studies involving missense mutation should also be performed.

Cord blood copeptin concentrations in fetal macrosomia.

Despina D Briana, Stavroula Baka, Maria Boutsikou +4 more

Excessive fetal growth is associated with increased adiposity and reduced insulin sensitivity at birth. Copeptin, a surrogate marker of arginine vasopressin (AVP) secretion, is upregulated in states of hyperinsulinemia and is considered one of the mediators of insulin resistance. We aimed to investigate cord blood concentrations of copeptin (C-terminal fragment of AVP pro-hormone) in healthy large-for-gestational-age (LGA) infants at term.

Effect of casein genes - beta-LGB, DGAT1, GH, and LHR - on milk production and milk composition traits in crossbred Holsteins.

A Molee, C Poompramun, P Mernkrathoke

The objectives of this study were to determine the effects of a single gene and composite genotype of the casein gene family, including the beta-lactoglobulin gene (beta-LGB), acyl-CoA: diacylglycerol acyltransferase 1 gene (DGAT1), growth hormone gene (GH), and luteinizing hormone receptor gene (LHR) on milk yield, milk composition, the percentage of fat, protein, solids-not-fat, and total solid in crossbred Holsteins. A total of 231 crossbred Holstein cows were examined for the study. The genotype of the beta-casein gene was analyzed by allele-specific polymerase chain reaction, while the alpha-S1, alpha-S2, kappa-casein, DGAT1, beta-LGB, and GH genes were analyzed using a polymerase chain reaction-restriction fragment length polymorphism assay. The association between genes and milk yield and milk composition was analyzed. Three pairs of genes, for which significant associations were detected, were beta + kappa-casein, DGAT1 + beta-casein, and GH + beta-LGB. In the single-gene model, most loci are significantly associated with traits. A significant association between the composite genotype and the traits was detected in all composite genotypes. GH + beta-LGB appears to be the most suitable variants for improving milk production and percentage of milk protein. Overall, the effects of the composite genotype and single gene were different. A physical or functional relationship between genes is necessary for investigating gene markers.

The Effects of a Single Developmentally Entrained Pulse of Testosterone in Female Neonatal Mice on Reproductive and Metabolic Functions in Adult Life.

Hyeran Jang, Shalender Bhasin, Tyler Guarneri +7 more

Early postnatal exposures to sex steroids have been well recognized to modulate predisposition to diseases of adulthood. There is a complex interplay between timing, duration and dose of endocrine exposures through environmental or dietary sources that may alter the sensitivity of target tissues to the exogenous stimuli. In this study, we determined the metabolic and reproductive programming effects of a single developmentally entrained pulse of testosterone (T) given to female mice in early postnatal period. CD-1 female mice pups were injected with either 5 μg of T enanthate (TE) or vehicle (control [CON] group) within 24 hours after birth and followed to adult age. A total of 66% of T-treated mice exhibited irregular cycling, anovulatory phenotype, and significantly higher ovarian weights than vehicle-treated mice. Longitudinal nuclear magnetic resonance measurements revealed that TE group had greater body weight, whole-body lean, and fat mass than the CON group. Adipose tissue cellularity analysis in TE group revealed a trend toward higher size and number than their littermate CONs. The brown adipose tissue of TE mice exhibited white fat infiltration with down-regulation of several markers, including uncoupling protein 1 (UCP-1), cell death-inducing DNA fragmentation factor, α-subunit-like effector A, bone morphogenetic protein 7 as well as brown adipose tissue differentiation-related transcription regulators. T-injected mice were also more insulin resistant than CON mice. These reproductive and metabolic reprogramming effects were not observed in animals exposed to TE at 3 and 6 weeks of age. Collectively, these data suggest that sustained reproductive and metabolic alterations may result in female mice from a transient exposure to T during a narrow postnatal developmental window.

Intrinsically disordered cytoplasmic domains of two cytokine receptors mediate conserved interactions with membranes.

Gitte W Haxholm, Louise F Nikolajsen, Johan G Olsen +7 more

Class 1 cytokine receptors regulate essential biological processes through complex intracellular signalling networks. However, the structural platform for understanding their functions is currently incomplete as structure-function studies of the intracellular domains (ICDs) are critically lacking. The present study provides the first comprehensive structural characterization of any cytokine receptor ICD and demonstrates that the human prolactin (PRL) receptor (PRLR) and growth hormone receptor (GHR) ICDs are intrinsically disordered throughout their entire lengths. We show that they interact specifically with hallmark lipids of the inner plasma membrane leaflet through conserved motifs resembling immuno receptor tyrosine-based activation motifs (ITAMs). However, contrary to the observations made for ITAMs, lipid association of the PRLR and GHR ICDs was shown to be unaccompanied by changes in transient secondary structure and independent of tyrosine phosphorylation. The results of the present study provide a new structural platform for studying class 1 cytokine receptors and may implicate the membrane as an active component regulating intracellular signalling.

Transcriptome analysis of the mammary gland from GH transgenic goats during involution.

Jian Lin, Ze Kun Bao, Qiang Zhang +3 more

Mammary glands are organs for milk production in female mammals. Growth hormone (GH) is known to affect the growth and development of the mammary gland, as well as to increase milk production in dairy goats. This study performed a comprehensive expression profiling of genes expressed in the mammary gland of early involution GH transgenic (n=4) and non-transgenic goats (n=4) by RNA sequencing. RNA was extracted from mammary gland tissues collected at day 3 of involution. Gene expression analysis was conducted by Illumina RNA sequencing and sequence reads were assembled and analyzed using TopHat. FPKM (fragments per kilobase of exon per million) values were analyzed for differentially expressed genes using the Cufflinks package. Gene ontology analysis of differentially expressed genes was categorized using agriGO, while KEGG pathway analysis was performed with the online KEGG automatic annotation server. Our results revealed that 75% of NCBI goat annotated genes were expressed during early involution. A total of 18,323 genes were expressed during early involution in GH transgenic goats, compared with 18,196 expressed genes during early involution of non-transgenic goats. In these expressed genes, the majority (17,589) were ubiquitously expressed in GH transgenic and non-transgenic goats. However, there were 745 differentially expressed genes, 421 of which were upregulated and 324 were downregulated in GH transgenic goats. GO and KEGG pathway analysis showed that these genes were involved in mammary gland physiology, including cell adhesion molecules, ECM-receptor interaction, Jak-STAT signaling pathway, and fat metabolism. Our results demonstrated that the GH receptor was strongly affected in GH transgenic goats, which may activate the IGF-1/Stat3 signaling pathway. Overall, our study provided a global view of the transcriptome during involution of GH transgenic and non-transgenic goats, which increases our understanding of the biology of involution in the goat.

The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

Kim Nuytens, Krizia Tuand, Quili Fu +5 more

Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea) have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH) genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH) signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women.

Miriam A Bredella, Anu V Gerweck, Lauren A Barber +4 more

Abdominal adiposity is associated with low BMD and decreased growth hormone (GH) secretion, an important regulator of bone homeostasis. The purpose of our study was to determine the effects of a short course of GH on markers of bone turnover and bone marrow fat in premenopausal women with abdominal adiposity.

Cell death and tissue reorganization in Rhynchosciara americana (Sciaridae: Diptera) metamorphosis and their relation to molting hormone titers.

Amanda Dos Santos Brandão, Jônatas Bussador do Amaral, Paula Rezende-Teixeira +3 more

Programmed cell death (PCD) is a focal topic for understanding processes underlying metamorphosis in insects, especially so in holometabolous orders. During adult morphogenesis it allows for the elimination of larva-specific tissues and the reorganization of others for their functionalities in adult life. In Rhynchosciara, this PCD process could be classified as autophagic cell death, yet the expression of apoptosis-related genes and certain morphological aspects suggest that processes, autophagy and apoptosis may be involved. Aiming to reveal the morphological changes that salivary gland and fat body cells undergo during metamorphosis we conducted microscopy analyses to detect chromatin condensation and fragmentation, as well as alterations in the cytoplasm of late pupal tissues of Rhynchosciara americana. Transmission electron microscopy and confocal microscopy revealed cells in variable stages of death. By analyzing the morphological structure of the salivary gland we observed the presence of cells with autophagic vacuoles and apoptotic bodies and DNA fragmentation was confirmed with the TUNEL assay in salivary gland. The reorganization of fat body occurs with discrete detection of cell death by TUNEL assay. However, both salivary gland histolysis and fat body reorganization occur under control of the hormone ecdysone.

Associations between insulin resistance, free fatty acids, and oocyte quality in polycystic ovary syndrome during in vitro fertilization.

Zhihong Niu, Nan Lin, Ruihuan Gu +2 more

Both polycystic ovary syndrome (PCOS) and obesity are associated with specific reproductive health complications, including lower oocyte quality and clinical pregnancy rates in assisted conception cycles, which may be a result of metabolism-induced changes in the oocyte through the microenvironment of follicular fluid. Free fatty acids (FFAs) are important biomedical indicators of abnormal lipid metabolism and have pronounced effects on cells, leading to changes in metabolism, cell growth, and differentiation.

Three new players in energy regulation: preptin, adropin and irisin.

Suleyman Aydin

Homeostasis of energy is regulated by genetic factors, food intake, and energy expenditure. When energy input is greater than expenditure, the balance is positive, which can lead to weight gain and obesity. When the balance is negative, weight is lost. Regulation of this homeostasis is multi-factorial, involving many orexigenic (appetite-stimulating) and anorexigenic (appetite-suppressing) peptide hormones. Peripheral tissues are now known to be involved in weight regulation and research on its endocrine characteristics proceeds apace. Preptin with 34 amino acids (MW 3948 Da), adropin with 43 amino acids and a molecular weight of (4999 Da), and irisin with 112 amino acids (12587 Da), are three newly discovered peptides critical for regulating energy metabolism. Preptin is synthesized primarily in pancreatic beta cells, and adropin mainly in the liver and brain, and many peripheral tissues. Irisin, however, is synthesized principally in the heart muscle, along with peripheral tissues, including salivary glands, kidney and liver. The prime functions of preptin and adropin include regulating carbohydrate, lipid and protein metabolisms by moderating glucose-mediated insulin release. Irisin is an anti-obesitic and anti-diabetic hormone regulating adipose tissue metabolism and glucose homeostasis by converting white to brown adipose tissue. This review offers a historical account of these discovery and function of these peptides, including their structure, and physiological and biochemical properties. Their roles in energy regulation will be discussed. Their measurement in biological fluids will be considered, which will lead to further discussion of their possible clinical value.

Glugacon-like peptide-2: broad receptor expression, limited therapeutic effect on intestinal inflammation and novel role in liver regeneration.

Noura El-Jamal, Edmone Erdual, Michel Neunlist +9 more

The glucagon-like peptide 2 (GLP-2) is an intestinotrophic hormone with growth promoting and anti-inflammatory actions. However, the full biological functions of GLP-2 and the localization of its receptor (GLP-2R) remain controversial. Among cell lines tested, the expression of GLP-2R transcript was detected in human colonic myofibroblasts (CCD-18Co) and in primary culture of rat enteric nervous system but not in intestinal epithelial cell lines, lymphocytes, monocytes, or endothelial cells. Surprisingly, GLP-2R was expressed in murine (GLUTag), but not human (NCI-H716) enteroendocrine cells. The screening of GLP-2R mRNA in mice organs revealed an increasing gradient of GLP-2R toward the distal gut. An unexpected expression was detected in the mesenteric fat, mesenteric lymph nodes, bladder, spleen, and liver, particularly in hepatocytes. In two mice models of trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis, the colonic expression of GLP-2R mRNA was decreased by 60% compared with control mice. Also, GLP-2R mRNA was significantly downregulated in intestinal tissues of inflammatory bowel disease patients. Therapeutically, GLP-2 showed a weak restorative effect on intestinal inflammation during TNBS-induced colitis as assessed by macroscopic score and inflammatory markers. Finally, GLP-2 treatment accelerated mouse liver regeneration following partial hepatectomy as assessed by histological and molecular analyses. In conclusion, the limited therapeutic effect of GLP-2 on colonic inflammation dampens its utility in the management of severe inflammatory intestinal disorders. However, the role of GLP-2 in liver regeneration is a novelty that might introduce GLP-2 into the management of liver diseases and emphasizes on the importance of elucidating other extraintestinal functions of GLP-2.

Association of HSL gene E1-c.276C>T and E8-c.51C>T mutation with economical traits of Chinese Simmental cattle.

X B Fang, L P Zhang, X Z Yu +4 more

Hormone-sensitive lipase (HSL) is responsible for the decomposition of triglycerides in adipose tissue to release free fatty acids, and it is a key rate-limiting enzyme in the regulation of adipose tissue deposition and decomposition. The objective of this study was to evaluate the association between novel SNPs in the coding region of bovine HSL gene and carcass and meat quality traits of Chinese Simmental-cross steers. Two novel SNPs were genotyped and the 47 traits of carcass and meat quality traits were measured in the population studied. Statistical analysis revealed that the SNPs of HSL gene were associated with the carcass and meat quality traits. The individuals with TT genotypes of E1-276C>T showed significant higher dressing percentage, net meat rate, hind legs circumference, fat coverage rate, mesenteric fat and kidney fat (p < 0.05). E8-51C>T (P17S) also showed a significant association with the pH of beef and fatty acids content in Chinese Simmental cattle (p < 0.01). Our findings indicated that polymorphisms in HSL might be one of important genetic factors that influence carcass yield and meat quality in beef cattle, and it may be a useful marker for meat quality traits in future marker-assisted selection programs in beef cattle breeding and production.

The effects of 11-ketotestosterone on ovarian physiology of previtellogenic captive hapuku (Polyprion oxygeneios).

Yair Y Kohn, Jane E Symonds, P Mark Lokman

The present study investigated, for the first time in a perciform teleost, the effects of in vivo 11-ketotestosterone (11-KT) treatment using slow-release implants on ovarian development and gonadotropin receptor mRNA levels in captive previtellogenic females of hapuku (Polyprion oxygeneios). At the cellular/functional level, ovarian development and ovarian and hepatic total lipid levels were examined. At the molecular level, transcript abundance of ovarian follicle-stimulating hormone receptor (FSH-R) and luteinizing hormone receptor (LH-R) was measured. Additionally, cyclic adenosine monophosphate (cAMP) levels in ovarian fragments from placebo and 11-KT implanted fish incubated with or without human chorionic gonadotropin (hCG) in vitro were compared between groups. There were no significant differences between treatments with regard to oocyte size and lipid contents of liver and ovary. Messenger RNA levels of FSH-R and LH-R were significantly lower in the treated females. Similarly, cAMP levels were significantly lower in the ovarian fragments of the 11-KT implanted females. These results suggest that 11-KT specifically, but possibly androgens in general, may not have an important function in regulating gonadal development of previtellogenic female hapuku; indeed, if anything, 11-KT appeared to have a detrimental effect and its use will not be beneficial in advancing sexual maturity of hapuku in aquaculture.

Genetic variants and effects on milk traits of the caprine paired-like homeodomain transcription factor 2 (PITX2) gene in dairy goats.

Haiyu Zhao, Xianfeng Wu, Hanfang Cai +4 more

The paired-like homeodomain transcription factor 2 (PITX2) gene plays a critical role in cell proliferation, differentiation, hematopoiesis and organogenesis. This gene regulates several genes' expressions in the Wnt/beta-catenin and POU1F1 pathways, thereby probably affecting milk performance. The goal of this study was to characterize the genetic variants of the PITX2 gene and test their associations with milk traits in dairy goats. Herein, four novel single nucleotide polymorphisms (SNPs), AC_000163:g.18117T>C, g.18161C>G, g.18322C>A and g.18353T>C, within the caprine PITX2 gene, were found in two famous Chinese dairy goat breeds. These SNPs mapping at Cys28Arg, Pro42Pro, IVS1+79C>A and IVS1+110T>C, were genotyped by the MvaI, SmaI, MspI and RsaI aCRS-RFLP or PCR-RFLP methods, respectively. Accordingly, two main haplotypes (CGCT and CGCC) were identified among the specimens. Association testing revealed that the SmaI and RsaI polymorphisms were significantly associated with the milk fat content, milk lactose content and milk density (P<0.05 or P<0.01) in the Guanzhong (GZ) dairy goats, respectively. At the same time, the RsaI locus was also found to significantly link to the second lactation milk yield, milk fat content, milk lactose content, milk density and milk total solid content (P<0.05 or P<0.01) in the Xinong Saanen (XNSN) dairy goats, respectively. These results indicated that the caprine PITX2 gene had the significant effects on milk traits. Hence, the RsaI and SmaI loci could be regarded as two DNA markers for selecting superior milk performance in dairy goats. These preliminary findings not only would extend the spectrum of genetic variation of the goat PITX2 gene, but also would contribute to implementing marker-assisted selection (MAS) in breeding and genetics in dairy goats.