Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spermatogenesis and spermiogenesis are controlled by FSH and testosterone but need also the participation of several paracrine and autocrine mechanisms of regulations. The relationships between peritubular, Sertoli and Leydig cells are currently investigated. High intratesticular testosterone levels are maintained by a binding to a protein called ABP which is synthetized by Sertoli cell and regulated by pituitary FSH. Leydig cell testosterone, peritubular cell P-Mod-S (protein modulating Sertoli function) and Sertoli cell FRP (follicle regulatory protein). Accumulation of testosterone results to aromatase activity modulation. Aromatization is stimulated by FSH, activin, alpha-MSH but is inhibited by aromatase inhibitor, inhibin, FSHBI (FSH binding inhibitor). Other molecules, growing factors, mitogenic factors, energetic substrates are synthetized in the testis under the control of germ cells. Understanding of these mechanisms of intratesticular regulation will permit to discover therapies capable of correcting certain fertility dysfunctions.
 ...
PMID:[Paracrine regulation of testicular function]. 265 82

Luteinizing hormone is the major regulator of Leydig cell differentiation and steroidogenic function. A number of hormones produced by the Leydig cell (e.g. estrogen, angiotensin, CRF, vasopressin) and the tubular compartment (inhibin, TGF beta), can influence both acute and long-term actions of LH. Conversely, hormones produced in the Leydig cells modulate tubular function (e.g. androgen, beta-endorphin, oxytocin). The LH stimulatory event can be negatively influenced by the action of angiotensin II through the guanyl nucleotide inhibitory unit of adenylate cyclase. We have recently discovered an action of corticotrophin releasing hormone through specific high-affinity low-capacity receptors in the Leydig cells which involves a pertussis toxin insensitive guanyl nucleotide regulatory unit with interaction between signalling pathways and resulting inhibition of LH induced cAMP generation and consequently of steroidogenesis. In contrast to other tissues the CRF receptor in the Leydig cells did not couple to Gs. CRF action is exerted through direct or indirect action of protein kinase C, at the level of the catalytic subunit of adenylate cyclase. Physiological increases in endogenous LH cause positive regulation of membrane receptors and steroidogenesis, while major elevations in circulating gonadotropin can induce down-regulation of LH receptors and desensitization of steroid responses in the adult cell. Gonadotropin-induced desensitization in adult rat tests include an estrogen mediated steroidogenic lesion of the microsomal enzymes 17 alpha-hydroxylase/17,20-desmolase. For further understanding of the regulation of this key enzyme of the androgen pathway the rat P450(17) alpha cDNA was cloned and sequenced. This cDNA expressed in COS-1 cells 17 alpha-hydroxylase/17,20-desmolase activities. From the deduced amino acid sequence, two transmembrane regions were identified, a signal peptide for insertion in the ER, and a 2nd transmembrane region separated from the first by 122 amino acids. The carboxy terminal non-transmembrane region possesses 4 hydrophobic clefts, of which cleft II would contain the putative steroid binding site for both hydroxylase and lyase activities. The rat cDNA was employed to evaluate the hormonal regulation of mRNA levels in adult and fetal Leydig cells. Low dose hCG treatment caused an early increase in mRNA levels followed by a return to control values at later times, while with higher desensitizing doses the initial increase in mRNA was followed by a marked reduction in mRNA at 24 h and a small recovery at 48 h. Fetal rat Leydig cells treated with E2 showed a 70% decrease in P450 mRNA levels, and testosterone production closely followed the changes in mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:LH action in the Leydig cell: modulation by angiotensin II and corticotropin releasing hormone, and regulation of P450(17) alpha mRNA. 269 45

It is well established that beta-endorphin has a regulatory influence on the reproductive function at the level of the hypothalamic-pituitary axis. However, recent immunohistochemical evidence demonstrated that beta-endorphin is also present in the Leydig cells of fetal, neonatal and adult mice and hamsters. In addition, beta-endorphin synthesis was localized in the Leydig cells of adult rats, leading to the hypothesis of a direct function of the peptide in the reproductive organs. Our interest was to investigate the role of beta-endorphin at testicular level. We have demonstrated the presence of high-affinity opioid binding sites (Kd in the nanomolar range) in tubular homogenates and Sertoli cells in culture of adult (50 days) and immature (18 days post-natal) rat testes. Also, chronic beta-endorphin treatment of the Sertoli cells significantly inhibited basal and FSH-stimulated androgen-binding protein production, this effect being prevented by the universal opiate antagonist naloxone. No opiate binding was observed on Leydig cell cultures. Furthermore, we have demonstrated that acute or chronic beta-endorphin treatment does not affect testosterone production by Leydig cells in vitro, consistent with the absence of receptors on these cells. On the other hand, fetal Leydig cells (21 days fetal life) in culture produced considerable amounts of beta-endorphin. Also, fetal Leydig cells represented a preferred in vitro system to study beta-endorphin release since in adult cell culture a marked degradation of the peptide was detected (greater than 50%). beta-endorphin accumulation for 3 and 5 days was markedly increased by inhibitors of steroid biosynthesis (1.5-fold); a significant reduction by GnRH at both days (by 50-30%) was observed, while by dexamethasone the reduction was only noted after 5 days of treatment (by 50%). Acute stimulation (3 h) of control cells with hCG enhanced by 10-12-fold the beta-endorphin secretion. The hormone stimulation of beta-endorphin production was not mediated by testosterone. On the contrary, inhibition of Leydig cells steroid biosynthesis markedly increased basal and hCG-stimulated beta-endorphin production (150-200%), suggesting autocrine negative modulation of Leydig cell beta-endorphin by androgen and/or its metabolites. In contrast, dexamethasone reduced basal and hCG-stimulated beta-endorphin production (by 50%). Altogether these findings indicate that beta-endorphin produced within the Leydig cells may behave as a paracrine inhibitor of the Sertoli cell function and demonstrate that the peptide production is under direct control by gonadotropins and is modulated by steroids.
 ...
PMID:Hormonal regulation of beta-endorphin in the testis. 283 95

Pro-opiomelanocortin (POMC)-derived peptides such as beta-endorphin, ACTH, and MSHs were identified in the testis where they were exclusively localized in Leydig cells. Examination of testicular extracts by a variety of physicochemical and immunological techniques indicates that the processing of the POMC in the testis is very similar to that in the brain. By using a cDNA probe, the POMC-like mRNA present in total testis and cultured Leydig cells was 150-200 bases shorter than that in the hypothalamus and pituitary. In addition, POMC mRNA was localized to Leydig cells using in situ hybridization. The expression of the POMC-like gene and the accumulation of POMC-derived peptides in Leydig cell were shown to be under the control of gonadotropin. As the testis contains low concentrations of POMC-derived peptides, we suggested that they may be implicated in local regulatory events within this organ. This postulate was supported by results from in vivo and in vitro experiments suggesting that different portions of the POMC-molecule may have opposite effects on Sertoli cell functions. For example, MSHs increased cAMP accumulation and aromatase activity in these cells, while opioids inhibited Sertoli cell proliferation and androgen binding protein (ABP) secretion. Furthermore, following intratesticular administration of opiate antagonists, testosterone production was reduced, suggesting that Leydig cell function may be also modulated by beta-endorphin and/or other related peptides. Taken together, these studies support the hypothesis of a possible role of POMC-derived peptides in testicular function.
 ...
PMID:Pro-opiomelanocortin-derived peptides in the testis: evidence for a possible role in Leydig and Sertoli cell function. 293 5

Immunohistochemical evidence has indicated that beta-endorphin (beta EP) is present in the Leydig cells of fetal, neonatal, and adult mice and hamsters. In vivo experiments suggest that hCG and/or testosterone may increase the synthesis and release of the peptide from the Leydig cell compartment. Since cultured fetal Leydig cells have considerable potential for long term studies and elucidation of trophic hormone actions in vitro, we evaluated beta EP production in this system. Fetal Leydig cells were maintained in culture for 5 days in medium with 1 microgram ovine LH added every third day in the presence or absence of inhibitors of cholesterol (aminoglutethimide) or pregnenolone metabolism (cyanoketone and spironolactone), or known regulators of beta EP production [dexamethasone (DEX)]. Media were assayed for testosterone and beta EP by RIA methods. Beta EP accumulation over 3 and 5 days was markedly increased by inhibitors of steroid biosynthesis (1.5-fold) and reduced by DEX only after treatment for 5 days (by 50%). Acute hCG stimulation significantly increased beta EP levels by 5- to 9-fold in all conditions tested. Inhibition of Leydig cell steroid biosynthesis markedly increased basal and hCG-stimulated beta EP output (by 150-200%). In contrast, DEX reduced basal and hCG-stimulated beta EP production (by approximately 50%). HPLC analysis of cultured pooled media revealed that the beta EP immunoreactivity eluted at the retention time of authentic rat beta EP. The pattern of beta EP stimulation was not reflected by testosterone levels that were low or undetectable in controls and under conditions in which spironolactone/cyanoketone or aminoglutethimide were present; most importantly, inhibition of steroid biosynthesis markedly increased beta EP levels. In addition, beta EP (10(-7) M) did not affect testosterone production, and opiate binding was not detected on Leydig cells. The lack of degradation of this opioid peptide in the fetal cultures contrasted with results from adult cultures and provided an ideal system for studies of the regulation of this peptide in Leydig cells. These results demonstrate that beta EP is released from fetal Leydig cells in culture and that acute stimulation of Leydig cells by hCG can enhance beta EP secretion. These changes are not mediated by testosterone. In contrast, testosterone or its metabolites may exert negative autocrine modulation of beta EP production.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Beta-endorphin production by the fetal Leydig cell: regulation and implications for paracrine control of Sertoli cell function. 296 54

It appears that the effect of acute administration of pituitary-adrenal hormones on the pituitary-gonadal axis is species-dependent. However, no information is available with regard to the effect of acute adrenocorticotropin (ACTH) administration on testosterone secretion in rats. The present data indicate that acute ACTH administration can increase serum testosterone levels without modifying luteinizing hormone (LH) levels. Since this rise was not observed in castrated rats, it must be assumed that increased serum testosterone was of gonadal origin. The action of ACTH on testosterone secretion was likely an indirect one since there is no evidence at present for a direct, short-term action of the pituitary-adrenal axis on Leydig cell function.
 ...
PMID:Adrenocorticotropin administration increases testosterone secretion in adult male rats. 301 12

The possible production of the opioid polypeptide beta-endorphin (beta-EP) was investigated in paraffin-embedded tissue from 17 ovarian tumors with the use of a specific anti-beta-EP antibody and the avidin-biotin-peroxidase staining technique. Only sex cord-stromal tumors (ten cases) showed positive staining. Strong beta-EP immunoreactivity was present in Leydig's cells of Sertoli-Leydig cell tumors; weaker sporadic staining was present in cells of granulosa cell tumors, and faint staining was present in occasional, luteinized theca cells of fibrothecomata. These findings suggest that cells with the sex cord-stromal phenotype that are capable of steroid production can also produce beta-EP. The latter may be a component of the "functional" status associated with some ovarian sex cord-stromal tumors and may serve as a helpful marker in distinguishing this type of tumors from germ cell or epithelial neoplasms.
 ...
PMID:Immunoreactive beta-endorphin in ovarian sex cord-stromal tumors. 303 26

Activation and regulation of Leydig cell function is exerted primarily by LH, which is secreted in pulses of high biological activity and interacts with membrane receptors. Other hormones and factors secreted by the Leydig cell or from the tubular compartment can influence Leydig cell differentiation and acute or chronic actions of LH on steroidogenesis. Conversely, hormones produced in the Leydig cell could modulate tubular function (e.g. beta-endorphin, oxcytocin). The LH receptor has been purified to homogeneity in sufficient quantities to allow its peptide sequence to be determined and its gene structure to be elucidated as well as functional reconstitution studies to be performed. The LH receptor subunit of Mr 90,000 can be phosphorylated by cAMP-dependent protein kinase. The native receptor appears to exist in the membrane as a dimer of identical subunits associated by noncovalent interactions. It is likely that receptor dimerization and further aggregation are necessary for signal transduction to occur, and receptor phosphorylation by one or more kinases may be involved in regulating gonadotropin action. Stimulation of the androgen pathway occurs mainly through a cAMP-mediated mechanism. The stimulatory event can be negatively influenced by the action of certain peptide hormones through the guanyl nucleotide inhibitory subunit of adenylate cyclase. Such an inhibitory action of angiotensin has further emphasized the importance of the cAMP pathway in the Leydig cell. The hormone also appears to facilitate androgen production by a cAMP-independent mechanism located at the plasma membrane or intracellular sites. A Ca2+ sensitive kinase system is present in the Leydig cell membranes. The presence of nM amounts of Ca2+ induces membrane phosphorylation of a protein Mr 45,000. Adenylate cyclase activation also is affected by Ca2+. Membrane phosphorylation may be a modifier of LH-stimulated adenylate cyclase activity and possibly other LH-induced actions in the activated Leydig cell membrane. In the adult rat testis, the ability of Leydig cells to respond to sustained gonadotropic stimulation with increased androgen production is limited by the development of a refractory state associated with loss of LH receptors and steroidogenic enzymes. Gonadotropin-induced steroidogenic lesions in adult rat testes include a late steroidogenic lesion at the site of conversion of progesterone to androgen and an early lesion before pregnenolone formation that leads to a decreased in vitro pregnenolone and testosterone response to hCG.
 ...
PMID:Endocrine regulation and communicating functions of the Leydig cell. 328 2

The POMC gene is expressed in testicular Leydig cells, but its mRNA is about 150-200 nucleotides shorter in these cells than in the pituitary. For this reason this testicular mRNA has been termed POMC-like mRNA. The purpose of the present study was to define the ontogeny and regulation of POMC gene expression in rat testis. The level of POMC-like mRNA was very low in the testes of 15- and 20-day-old animals. A dramatic increase in mRNA concentration was observed between 20 and 25 days of age, and maximal levels were detected at 40 days. The ontogeny of testicular POMC gene expression correlates with the reported increases in Leydig cell numbers, immunostainable beta-endorphin in Leydig cells, and testicular LH receptors during development. Since these observations suggested that the expression of testicular POMC gene might be influenced by LH, we studied the effect of hypophysectomy and hCG treatment on testicular POMC-like mRNA. Total contents of testicular RNA and POMC-like mRNA decreased in parallel with the decline of testicular weight after hypophysectomy. Administration of hCG to rats 6 days after hypophysectomy prevented the regression of testes and the decrease in testicular POMC-like mRNA content. An increase in the total amount of testicular POMC-like mRNA was observed relative to that in hypophysectomized controls after 8 days of hCG injection. Similar results were obtained when hCG was administered to rats 13 days after hypophysectomy. The effect of glucocorticoid deprivation on testicular POMC-like mRNA was also studied. The POMC-like mRNA concentration did not increase in testis as it did in the anterior pituitary after adrenalectomy, suggesting that glucocorticoids are not a primary regulator of POMC-like mRNA in the testis. In summary, the ontogeny of expression of testicular POMC gene correlates closely with the maturation pattern of Leydig cells; and the expression of testicular POMC gene is regulated by gonadotropins and not by glucocorticoids. We conclude that the regulation of POMC-like mRNA in the testis is different from that in the pituitary.
 ...
PMID:Regulation of testicular proopiomelanocortin gene expression. 359 33

Eight ovarian heterologous Sertoli-Leydig cell tumors containing gastrointestinal-type cells, including two tumors that contained carcinoids, were stained for argyrophilia and argentaffinity; in addition, these specimens were stained by immunohistocytochemical techniques for the demonstration of chromogranin, serotonin, and a variety of peptide hormones. Intestinal- and gastric-type epithelial and carcinoid cells within the tumors were focally argyrophilic and chromogranin-positive, but only intestinal-type epithelial and carcinoid cells contained argentaffin granules, serotonin, and corticotropin. Somatostatin, gastrin, neurotensin, and glucagon were demonstrated additionally in varying numbers of specimens containing intestinal-type epithelium and carcinoid, and somatostatin was present in gastric-type epithelium in one case. Staining for calcitonin and insulin was negative. Despite the frequent identification of serotonin and peptide hormones in the tumors in the present series, evidence of the carcinoid syndrome or syndromes associated with peptide hormone excess was lacking on review of the patients' records.
 ...
PMID:Ovarian heterologous Sertoli-Leydig cell tumors with gastrointestinal-type epithelium. An immunohistochemical analysis. 375 27


<< Previous 1 2 3 4 Next >>