Atrazine and the Hypothalamo-Pituitary-Gonadal Axis in Sexually Maturing Precocial Birds

The herbicide atrazine is a putative endocrine disruptor. The present studies investigated the effects of atrazine in male Japanese quail during sexual maturation. Atrazine was administered for 2 weeks in the diet or systemically to birds under long photoperiods. Atrazine had no effect on mortality but depressed both feed intake and growth (average daily gain [ADG] in g/day) at dietary concentrations of 1000 ppm. Atrazine in the diet at 10 ppm, but at no other concentrations, increased testes weight and gonadal-somatic-index and decreased the seminiferous tubule diameter-to-testis weight ratio. Atrazine in the diet at 1000 ppm increased circulating concentrations of testosterone. Dietary atrazine at 10 ppm increased circulating concentrations of estradiol. Atrazine administered systemically exerted no effect on indices of growth or reproduction. Atrazine did not mimic the effects of either estradiol or tamoxifen in male quail; thus, atrazine did not exhibit overt estrogenic or anti-estrogenic activity. It is concluded that atrazine up to 1000 ppm in the diet may exert some effects on reproductive development in sexually maturing male birds, but these are inconsistent and modest

Perspectives on Endogenous Opioids in Birds

The present review summarizes the state of knowledge of endogenous opioids in birds. Endogenous opioid peptides acts in a neuromodulatory, hormonal and paracrine manner to mediate analgesic and other physiological functions. These peptides act through specific G-protein coupled receptors. Opioid receptors consist of a family of four closely-related proteins. The three types of opioid receptors are the mu (MOR or μ), delta (DOR or δ), and kappa (KOR or κ) opioid receptor proteins. The role of the fourth member of the opioid receptor family, the nociceptin or orphanin FQ receptor (ORL), is not clear. The ligands for opioid receptors are: β –endorphin (MOR), Met- enkephalin, Leu-enkephalin (DOR) and dynorphin (KOR), together with probably endomorphins 1 and 2. In spite of long history of research on endogenous opioid peptides, there are no studies of endogenous opioids per se in wild birds and few in poultry species. β-endorphin is present in all birds investigated and there is close agreement between the structures of β-endorphin in different birds. Plasma concentrations of β-endorphin are increased by ether stress in geese. There is evidence that β-endorphin plays a role in the control of luteinizing hormone release in chickens. Met-enkephalin is present in tissues such as the retina, hypothalamus, pituitary gland, and adrenals together with circulation of birds. Stresses such as crowding and withholding water increase circulating concentrations of Met-enkephalin in chickens. The structures of chicken dynorphin A and B have been deduced from cDNA. What is missing are comprehensive studies of plasma concentrations and expression of the full array of endogenous opioids in multiple avian species under different situations. Also, what is not known is the extent to which circulating or locally released or intra-cellular Met-enkephalin influence physiological process in birds. Thus, there is considerable scope for investigation of the physiology of endogenous opioids in birds

Ghrelin Stimulates Porcine Somatotropes

Ghrelin is an endogenous ligand for growth hormone secretagogue receptor (GHS-R) and is predominantly produced by the stomach and lower amounts in the hypothalamus and various peripheral tissues. Ghrelin is a potent stimulator of growth hormone (GH) secretion from the pituitary in vivo and in vitro. GH secretion from the pituitary also is controlled by two hypothalamic peptides: stimulatory GH-releasing hormone (GHRH) and inhibitory somatostatin-14 (SRIH). GH participates in its own rhythmic secretion through feedback action on GHRH and SRIH neurons. The mechanism of action of GHS is not established. The present study examined the signal transduction pathways of ghrelin in isolated porcine somatotropes. The ability of ghrelin to induce an increase in the intracellular Ca2+ concentration – [Ca2+]i – somatotropes was examined in dispersed porcine pituitary cells using a calcium imaging system. Somatotropes were functionally identified by application of human growth hormone releasing hormone (hGHRH). Ghrelin increased the [Ca2+]i in a dose-dependent manner in 98% of the cells that responded to. In the presence of (D-Lys3)-GHRP-6, a specific receptor antagonist of GHS-R, the increase in [Ca2+]i evoked by ghrelin was decreased. Pretreatment of cultures with somatostatin or neuropeptide Y reduced the ghrelin-induced increase of [Ca2+]i. The stimulatory effect of ghrelin on somatotropes was greatly attenuated in lowcalcium saline and blocked by nifedipine, an L-type calcium channel blocker, suggesting involvement of calcium channels. In a zero Na+ solution, the stimulatory effect of ghrelin on somatotropes was decreased, suggesting that besides calcium channels, sodium channels are also involved in ghrelin-induced calcium transients. Either SQ-22536, an adenylyl cyclase inhibitor, or U73122, a phospholipase C inhibitor, decreased the stimulatory effects of ghrelin on [Ca2+]i transiently, indicating the involvement of adenylyl cyclase-cyclic adenosine monophosphate and phospholipase C inositol 1,4,5-trisphosphate pathways. The non-peptidyl GHS, L-692,585 (L-585), induced changes in [Ca2+]i similar to those observed with ghrelin. Application of L-585 after ghrelin did not have additive effects on [Ca2+]i. Preapplication of L-585 blocked the stimulatory effect of ghrelin on somatotropes. Our results suggest that the actions of ghrelin and synthetic GHS closely parallel each other, in a manner that is consistent with an increase of hormone secretion. An understanding of the molecular mechanisms by which ghrelin and GHS modulate GH secretion is of particular interest in the regulation of GH for muscle accretion and somatic growth

Subpopulations of Chicken Somatotropes with Differing Intracellular Calcium Concentrations Responses to Secretagogues

Multiple secretagogues stimulate the release of growth hormone (GH). The present studies examined the ability of chicken somatotropes to respond to GH secretagogues with increased intracellular calcium concentrations ([Ca 2+ ]i ). It was hypothesized that there are subsets of the somatotrope population with different responsiveness to the various secretagogues. Avian somatotropes were identified and distinguished from other anterior pituitary cells, by their unique ability to respond to GH-releasing hormone with increased [Ca 2+ ]i with immunocytochemistry used as a post-hoc confirmatory test. Large increases in [Ca 2+ ]i (222 ± 16 nm) were evoked by thyrotropin-releasing hormone in only 73% of the somatotropes. Similarly, [Ca 2+ ]i was increased by perifusion with pituitary adenylate cyclase-activating peptide in 85% and by leptin but only in 51% of somatotropes. Ghrelin acutely increased [Ca 2+ ]i in only 21% of somatotropes. Perfusion with gonadotropinreleasing hormone elevated [Ca 2+ ]i , but in only 40% of somatotropes. The kinetics of calcium transients and the magnitude of the response differed from those observed in the presumptive gonadotropes. It is concluded that there are subsets of the somatotrope population in the anterior pituitary gland with differences in their ability to respond to various secretagogue

Opioid-like peptides and ghrelin mitigation of bariatric results depends on obesity level

Introduction: Bariatric surgery, as the only effective treatment of obesity, has strong effects on the metabolism, and nervous and endocrine systems. Thus, based on the different opinions about the efficaciousness of morbid obesity treatments, the aim of the present study was to estimate the association of serum ghrelin and Met-enkephalin (native, five amino acids and cryptic, precursor of enkephalin) concentrations with body mass index (BMI) value in bariatric patients within 30 postoperative days. Material and methods: The study was performed on 38 female patients divided into two groups: I — BMI lower than 40 kg/m2 (n = 18) and II — BMI higher than 40 kg/m2 (n = 20). Blood was taken before (–24 h), and 72 h and 30 days after the sleeve gastrectomy. Routine haematological, anthropometric, and metabolic parameters as well as thyroid-stimulating hormone (TSH), ghrelin, and Met-enkephalin values were measured in all patients. Results: There were statistically significant differences between the two groups before the surgery in terms of TSH, both forms of Metenkephalin, triglycerides concentrations, and activity of alanine transaminase (ALT), gamma glutamyltransferase (GGTP), and C-reactive protein (CRP). After 72 h, the serum levels of cryptic Met-enkephalin and CRP, and activity of enzymes varied between the two groups of patients. Thirty days after the surgery, some metabolic and immune parameters were still different in both female groups in favour of patients with lover BMI. However, significant differences were noticed in the levels of ghrelin (increase), and native (decrease) and cryptic Met-enkephalins (increase). Conclusions: The activity of endogenous peptides in bariatric patients is connected with the degree of obesity. Ghrelin level increases are negatively correlated with native Met-enkephalin changes shortly after bariatric surgery. The interplay of ghrelin and opioids might be considered as a predictor of postoperative weight loss success.

Endokrynne implikacje otyłości i zabiegów bariatrycznych

Otyłość jest szeroko rozpowszechnioną w świecie chorobą związaną z zaburzeniami układu endokrynnego. W ostatnich latach przeważa opinia, że jedynym skutecznym sposobem leczenia otyłości jest zabieg bariatryczny. Dlatego też celem niniejszej pracy przeglądowej było porównanie publikowanych w ciągu ostatniej dekady poglądów na hormonalną regulację apetytu, przyczyn rozwoju otyłości i procedur bariatrycznych. Publikacje zostały wybrane pod kątem: 1. przyczyn i konsekwencji otyłości, głównie zaburzeń hormonalnych; 2. rozwoju metod bariatrycznych, począwszy od pierwszej do obecnie stosowanych i perspektywicznych mniej agresywnych; 3. oceny wpływu zabiegów bariatrycznych na endokrynny status pacjenta. Najczęściej występującymi hormonalnymi zaburzeniami kojarzonymi z otyłością są: dysfunkcja podwzgórzowych szlaków związanych z pobieraniem pokarmu, insulinooporność, zmiany aktywności hormonów jelitowych i patologiczna aktywność hormonalna adipocytów. Obecnie najbardziej rekomendowane procedury bariatryczne to laparoskopowe wyłączenie żołądkowo-jelitowe na pętli Roux-en-Y, mankietowa resekcja żołądka, regulowana opaska żołądkowa. Procedury bariatryczne, głównie kombinacje restrykcyjne i ograniczające wchłanianie, obniżają masę ciała i eliminują wiele, ale nie wszystkie komponenty syndromu metabolicznego. Wnioski: 1. Głód i sytość regulowane są przez interakcję nerwowych i endokrynnych sygnałów. 2. Wydzielanie adipokin ze zdrowej tkanki tłuszczowej warunkuje stan przeciwzapalny, zwiększenie insulinowrażliwości i działanie kardioprotekcyjne. Przy zwiększonej objętości tkanki tłuszczowej adipokiny mają działanie prozapalne, aterogenne, mogą wywołać insulinooporność i ogólnie negatywne zmiany systemowe. 3. Zabiegi bariatryczne nie są rozwiązaniem dla wszystkich otyłych pacjentów. 4. Długotrwała, pozabiegowa obserwacja zmian profilu hormonalnego jest niezbędna i powinna być obligatoryjna