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

Gene expression of mouse testicular germ cells and surrounding somatic cells during spermatogenesis was examined by RNA:cDNA hybridization in situ and concomitant Northern and dot blot analysis. Particular attention was paid to obtaining fixation and hybridization procedures for use with mouse testes to accomplish sensitive and precise localization with the in situ technique. alpha-Tubulin mRNAs were localized in virtually all testis cell types. In elongating spermatids, a unique labeling pattern was visualized; possibly corresponding to the position of the asymmetrically displaced cytoplasm. Pro-opiomelanocortin (POMC) transcripts in the adult mouse testis detected by Northern blot analysis were shown to be of a smaller size (approximately 600-800 nt) than the pituitary POMC transcripts, similar to what has been reported recently for POMC expression in the rat testis and mouse Leydig cell lines. Localization of POMC mRNAs by in situ hybridization was primarily to Leydig cells, although some labeling of spermatogonia and spermatocytes within the seminiferous epithelium was detected. A cellular or developmental specificity of the pattern of POMC localization was observed: obvious labeling of Leydig cells was limited to interstitial regions which were surrounded completely or in part by tubules in stages IX to XII of the cycle of the seminiferous epithelium.
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PMID:Localization of mRNAs in mouse testes by in situ hybridization: distribution of alpha-tubulin and developmental stage specificity of pro-opiomelanocortin transcripts. 404 22

Using antibodies against peptides derived from different portions of the POMC molecule, immunocytochemical evidence suggests that this precursor and/or the peptides present within it are localized in testicular Leydig cells of at least five species. There is no evidence for the localization of these peptides or their precursor in any other cell type in this organ. Examination of testicular extracts by gel filtration, SDS-PAGE, and RP-HPLC indicate that the testis contains low concentrations of POMC-derived peptides relative to brain. Further analysis indicates that POMC is processed to alpha-MSH and beta-endorphin similar to its processing in intermediate pituitary lobe and brain. The relative mobilities of immunoreactive alpha-MSH and beta-endorphin on RP-HPLC columns indicate that they are in the unacetylated state as in brain and in contrast to the acetylated forms in the intermediate pituitary lobe. The potential for Leydig cells to synthesize POMC and its peptides was suggested by the demonstration of POMC-like mRNA in total testis and Leydig cell cultures. The size of the POMC-like mRNA is approximately 150 base pairs shorter than anterior or intermediate pituitary POMC mRNA. POMC-like mRNA activity has also been localized to Leydig cells in sections of testes using in situ hybridization. Immunostainable beta-endorphin and other POMC-derived peptides are present in testicular Leydig cells during fetal life and following puberty at times when testosterone secretion is maximal. The accumulation of immunostainable POMC-derived peptides in Leydig cells is dramatically increased by LH and hCG. A variety of observations suggests that testicular cells can respond to POMC-derived peptides. ACTH and the MSHs stimulate growth and cAMP accumulation in Sertoli cells. By contrast, studies using antagonists suggested that beta-endorphin and/or another testicular opioid inhibit Sertoli cell proliferation and ABP secretion. These observations are consistent with the postulate that different portions of the POMC molecule may have opposite effects on Sertoli cell function and suggest a mechanism by which Leydig cells could modulate Sertoli cell activity. Intratesticular administration of opiate antagonists inhibits testosterone secretion both in vivo and in vitro. These observations suggest that Leydig cell-derived beta-endorphin may facilitate testosterone secretion either directly or indirectly. The finding of POMC and its derivative peptides in testis, ovary, adrenal, and placenta suggests that all steroid hormone-secreting organs in mammals may utilize this peptidergic system.
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PMID:Identification and possible function of pro-opiomelanocortin-derived peptides in the testis. 610 19

Adrenocorticotropin (ACTH), beta-endorphin, and the melanocyte-stimulating hormones (MSHs), which are products of a common precursor, pro-opiomelanocortin (POMC), are present in a variety of tissues other than pituitary. The recent detection of immunoreactive POMC-derived peptides in the male reproductive tract raised the possibility that these hormones might regulate reproductive function. To determine whether the low concentrations of POMC-derived peptides in the male reproductive tract are synthesized locally and are not contaminants from blood, we have demonstrated POMC-like gene expression in both testis and epididymis. The identification of cells in testis capable of synthesizing POMC mRNA was established by showing the presence of this mRNA in mouse Leydig cell lines (TM3 and I10A). The hybridizing species of POMC-like mRNA in the testis, epididymis, and Leydig cell lines (TM3 and I10A) were approximately 150 bases shorter than those in the pituitary or hypothalamus but were similar in size to that in the amygdaloid nucleus of rat brain. The concentration of POMC-like mRNA in the testis is almost as high as that in the hypothalamus. This finding is quite unexpected because the concentrations of POMC-derived peptides in the testis were 2-3 orders of magnitude lower than those in the hypothalamus. The demonstration of a POMC-like gene expression in male reproductive tissues suggests that POMC-derived peptides are synthesized in Leydig cells and epididymis. These observations are consistent with the postulate that POMC-derived peptides may exert paracrine and/or autocrine effects in these organs.
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PMID:Expression of pro-opiomelanocortin-like gene in the testis and epididymis. 620 26

During the human aging process, basal plasma levels of cortisol and aldosterone demonstrate little change, while concentrations of adrenal androgens (AA) such as dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and androstenedione (A) decrease dramatically in men and women. There is no age-related change in ACTH concentrations to explain this observation. In this study, ACTH (cosyntropin, alpha1-24 corticotropin) stimulation tests were performed on elderly subjects and controls to test the hypothesis that analogous to the aging testicular. Leydig cell, AA-producing cells of the aging adrenal gland may become less sensitive to physiological levels of ACTH, but still retain their sensitivity to elevated ACTH levels. Results showed that in the elderly subjects, basal levels and ACTH-stimulatability of cortisol and aldosterone were unchanged. In agreement with earlier studies, basal levels of AA were found to be decreased in the elderly. However, ACTH stimulation demonstrated impaired reserve in DHA and A, and a total lack of stimulatability of DHAS. These findings could be explained by an age-related loss of adrenal enzymes or cell populations which produce AA, a loss or decrease in a subpopulation of ACTH receptors specific for AA production, or loss of a pituitary factor necessary for AA secretion.
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PMID:Decreased adrenal androgen sensitivity to ACTH during aging. 626 2

An 11-year-old patient with male pseudohermaphroditism presented with essentially normal-appearing female external genitalia. When examined, inguinal gonads, redundant foreskin, and some posterior labial fusion were found. Evaluation revealed basal testosterone (T) levels ranging from 65 to 107 ng/dl with slightly elevated serum gonadotropin levels (luteinizing hormone [LH]: 76 ng/ml, and follicle-stimulating hormone [FSH]: 568 ng/ml). Neither T nor its precursors increased with human chorionic gonadotropin (hCG) stimulation. However, progesterone (P), 17-hydroxyprogesterone (17-OHP), and cortisol (F) responses to adrenocorticotropic hormone (ACTH) were normal. Androgen binding and 5 alpha-reductase activity in cultured genital skin fibroblasts were normal. These data, plus the microscopic finding of a markedly reduced number of Leydig cells, strongly suggest that the male pseudohermaphroditism in this patient was due to inadequate Leydig cell function unrelated to LH receptors.
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PMID:Leydig cell hypofunction resulting in male pseudohermaphroditism. 628 Oct 87

A 27 year old nulliparous woman with a history of chronic anovulation and signs of virilization with a markedly elevated serum level of testosterone, underwent a laparotomy with peroperative bilateral ovarian vein catheterization and bilateral bisection of both ovaries. A solid, 1.5 cm, well delimited tumor located centrally in the right ovary, was excised. Testosterone levels in ovarian venous blood from the tumor bearing side, were 88.4 nmol/l and from the contralateral ovary 3.9 nmol/l. Histopathological examination showed a Sertoli-Leydig cell tumor which was radically extirpated. Postoperatively, the serum levels of androgen normalized, the woman had regular cycles, became pregnant and delivered a normal female baby. Pieces of tumor tissue were incubated for 2 h, with and without addition of gonadotropins and adrenocorticotropic hormone (ACTH). Human chorionic gonadotropin (CG), follicle stimulating hormone (FSH) and adrenocorticotropic hormone (ACTH) caused significant increases in cyclic monophosphate (cAMP) production in tumor tissue in vitro, as compared to controls. Furthermore, ACTH also significantly stimulated 17 beta-estradiol production. In tumor cells cultured for 48 h, FSH slightly, but not significantly, increased the production of progesterone. In the cell culture, [3H]-thymidine incorporation into deoxyribonucleic acid (DNA) was stimulated by IGF1 alpha but not by hCG and FSH. It is concluded that Sertoli-Leydig cell tumors may be sensitive to gonadotropins and ACTH and that their small size, solid shape and intra-ovarian localization can cause diagnostic difficulties.
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PMID:In vitro production of cyclic AMP and steroids from an ovarian Sertoli-Leydig cell tumor. Notes on clinical management. 773 6

The birth of an infant with ambiguous genitalia constitutes a medical emergency. Ill infants with ambiguous genitalia often require blood transfusions. We studied steroid levels in packed red blood cells from 10 healthy adult donors to determine whether packed red blood cells contain significant amounts of donor steroids that might interfere with hormonal testing. Levels of cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, aldosterone, and dihydrotestosterone were well below normal newborn values. Hemolyzed packed red blood cells were used to provide the maximum possible donor steroid contribution. The concentration of testosterone was substantial in hemolyzed packed red blood cells but was effectively reduced to below normal female newborn levels by washing packed red blood cells by a standard blood bank procedure. Corticotropin testing for evaluation of adrenal function can be done accurately, even in infants receiving frequent transfusions of packed red blood cells. To avoid any misinterpretation of testosterone levels, it might be prudent to use washed packed red blood cells during human chorionic gonadotropin testing to evaluate Leydig cell function.
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PMID:Effect of frequent blood transfusions on steroid determinations in newborn infants. 806 22

Corticotropin-releasing factor (CRF), the key neuropeptide in the stress cascade, has major inhibitory actions on testicular function in addition to its known antireproductive effects at the central level (inhibition of sexual behavior and LH secretion). CRF is secreted by the Leydig cells of the testis and acts through high-affinity receptors at the Leydig cell membrane as a potent negative regulator of LH action, inhibiting gonadotropin-induced cAMP generation and androgen production. CRF is also a primary stimulus of beta-endorphin secretion by the Leydig cells, which in turn exerts paracrine inhibition of FSH action in the tubular compartment of the testis through high-affinity receptors in the Sertoli cells. CRF action in the Leydig cells involves a pertussis toxin-insensitive guanyl nucleotide regulatory unit. In contrast to CRF receptors in the brain, pituitary, and other peripheral tissues, those in the Leydig cell are not coupled to Gs. The inhibitory action of CRF in the Leydig cell is exerted through protein kinase C, at the level of the catalytic subunit of adenylate cyclase. The secretion of CRF by the Leydig cell is stimulated by LH, acting via release of serotonin (5HT) and autocrine activation of 5HT2 receptors. Serotonin acts on 5HT2 receptors in the Leydig cell to stimulate CRF secretion via a pertussis toxin insensitive G-protein and presumably through activation of phosphoinositide hydrolysis. The diversity of the biochemical responses to CRF and 5HT2 receptor activation (i.e., inhibition of adenylate cyclase at the cytoplasmic aspect of the cell membrane vs. stimulation of CRF release from secretion granules) may reflect the stimulation of different protein kinase C isoenzymes. The LH-->5HT-->CRF inhibitory loop serves to continuously buffer the stimulation of androgen production by gonadotropin. 5HT, the immediate stimulus of testicular CRF secretion, is released during stress and is locally increased in the testis in pathological conditions associated with impaired testicular function (i.e., orchitis, varicocele). Also, propranolol, the beta-adrenergic antagonist frequently used in the control of blood pressure in patients with hypertension and often associated with impotence, acts via a serotonergic mechanism to stimulate CRF secretion and causes marked inhibition of LH-induced cAMP production and steroidogenesis in cultured Leydig cells. These basic studies of 5HT and CRF are relevant to the pathogenesis of testicular dysfunction and for the development of antagonist therapies to block CRF production and its local antireproductive effects.
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PMID:Corticotropin-releasing factor: an antireproductive hormone of the testis. 838 38

This study examined the potential role of testicular opioids, a pertussis toxin (PT)-sensitive G-protein, and phosphodiesterase in mediating the inhibitory effect of immobilization stress on testicular steroidogenesis in adult rats. The experiments were initiated with enriched preparations of Leydig cells, but the stress effect was not sustained in vitro either as a result of the disruption of the morphology of the testis and/or the time required for Leydig cell isolation. Consequently, testicular fragments from control and stressed (3-hour immobilization) rats were used in these experiments. When fragments from stressed rats were incubated for 2 hours in the absence and presence of human chorionic gonadotropin (hCG) (0.1,1, or 10 mlU), testosterone (T) production in response to 1 and 10 mlU hCG was lower (P < 0.05 and 0.01, respectively) than that from control fragments. Basal T secretion did not differ between stressed and control fragments. Naloxone (1, 10, or 100 mu M), did not alter basal or hCG-stimulated T secretion from control fragments, but it normalized the T response to hCG from stressed fragments. Control fragments also showed a reduced T response (P < 0.05) to hCG in the presence of beta-endorphin (beta-E; 36 nM). Incubation of control fragments with PT (30 ng) did not alter basal or hCG-stimulated T production. However, PT normalized (P < 0.01) hCG-stimulated T secretion from stressed fragments. Methylisobutylxanthine (MIX; 0.125 mM) elevated (P < 0.01) hCG-stimulated T production from control fragments, but hCG-stimulated T secretion from stressed fragments remained subnormal in the presence of the phosphodiesterase inhibitor. The data suggest that acute immobilization stress inhibits gonadotropin-induced T production in adult male rats via a mechanism involving testicular opioids and a PT sensitive G-protein. We found no evidence to suggest that a stress induced increase in the activity of phosphodiesterase was involved in this mechanism.
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PMID:Mechanism of stress-induced attenuation of the testicular response to gonadotropin: possible involvement of testicular opioids, a pertussis toxin-sensitive G-protein, and phosphodiesterase. 883 36

The effect of VIP on mast cell invasion/degranulation in testicular interstitium of stressed (immobilization and cold) and beta-endorphin-treated rats were investigated. Fifty-three Wistar male rats were used in four series of experiments. Initially, the effect of immobilization and cold stress on mast cell invasion and degranulation in testicular interstitium was examined in three age group of rats: 15 (n = 6), 30 (n = 6), and 45 (n = 7) days of age. Five animals per age group were used as controls. Because the most obvious effect of the stress on mast cell invasion/degranulation in testicular interstitium was observed in 45-day-old rats, the action of VIP in stressed and beta-endorphin-treated rats was only investigated at this age group. Mast cells and Leydig cells were evaluated by using histochemical and light microscopic protocols. Stress caused mast cell accumulation and degranulation in the testicular interstitium. Stress decreased heparin synthesis and possibly increased histamine content of mast cells. The effect of beta-endorphin was not as high as seen with stress. In some areas of testicular interstitium of stressed rats, there were aplasic and/or inactive Leydig cells. VIP inhibited proliferation and degranulation of mast cells, increased heparin content of the cells, and protected Leydig cells. By way of mast cell accumulation and degranulation in the testicular interstitium, exposure to stress may lead to Leydig cell damage and infertility. VIP may be involved in the protection of normal testicular function under stress conditions.
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PMID:The effect of vasoactive intestinal peptide (VIP) on mast cell invasion/degranulation in testicular interstitium of immobilized + cold stressed and beta-endorphin-treated rats. 884 72


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