Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stimulatory effects on Leydig cell testosterone secretion of a polypeptide(s) factor present in testicular interstitial fluid (IF) were compared with those of hCG and an LHRH agonist (LHRH-A). The actions of IF and LHRH-A were similar in showing (1) a delayed onset of action, (2) enhancement of testosterone production in response to a maximally stimulating concentration (5 nM) of hCG, and (3) near cessation of stimulation following their removal from the incubation medium. However, addition of an LHRH antagonist blocked only the actions of LHRH-A. Moreover, IF continued to stimulate testosterone production up to at least 20 h either on its own or in the presence of 5 nM hCG, whereas the stimulatory effects of LHRH-A disappeared beyond 6 h. IF was also able to enhance testosterone production in response to LHRH-A or in response to hCG + LHRH-A. IF enhanced testosterone production over 4-20 h in response to all doses of hCG and increasing concentrations of IF caused dose-dependent increments in the rate of hCG (5 nM) stimulated testosterone production. With submaximally stimulating doses of hCG or with LHRH-A alone, the stimulatory effect of IF was more or less additive, whereas with maximally stimulating doses of hCG the effect of IF was clearly synergistic. Thus, whereas the rate of testosterone production by Leydig cells in response to 5 nM hCG declined progressively from 4 to 20 h, addition of IF attenuated or prevented this decline. These findings have implications with respect to the physiological control of intratesticular testosterone levels and with respect to the regulation of steroidogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1985 Jul
PMID:Intratesticular regulation of testosterone secretion: comparison of the effects and interactions of hCG, an LHRH agonist and testicular interstitial fluid on Leydig cell testosterone secretion in vitro. 316 Jun 20

We have studied the effects of human interleukin-1 beta on steroidogenesis in cultured immature rat Leydig cells. In the presence of low concentrations of LH or in its absence interleukin-1 beta markedly stimulates the production of C19-steroids (testosterone and androstenedione) and C21-steroids (progesterone, 17 alpha-hydroxyprogesterone, 20 alpha-hydroxypregn-4-en-3-one). In the presence of maximally effective concentrations of LH, on the contrary, interleukin-1 beta inhibits C19-steroid production by provoking a block at the level of the 17,20-desmolase. These actions were observed with similar low doses of interleukin-1 beta (ED50 = 1 U/ml), but the stimulatory effects are evident within the first 2 h of incubation whereas the inhibitory actions appeared after a latent period of 6 h. None of the effects of interleukin-1 beta is accompanied by measurable changes in cAMP output, and the effects are much less pronounced in freshly isolated Leydig cells than in cultured cells. At maximally effective doses the effects of interleukin-1 beta are additive with those of a number of other Leydig cell agonists: LHRH, epidermal growth factor, arginine vasopressin and Sertoli cell-derived factor(s), suggesting that these agonists act by mechanisms different from that of interleukin-1 beta. The possibility is considered that Leydig cells may act as target cells for interleukin-1 beta derived from testicular macrophages or for interleukin-1-like factors derived from testicular tubules.
Mol Cell Endocrinol 1988 May
PMID:Interleukin-1 stimulates steroidogenesis in cultured rat Leydig cells. 326 Aug 76

ProLHRH contains the luteinizing hormone-releasing hormone (LHRH) decapeptide and a 56 amino acid peptide designated gonadotropin-releasing hormone-associated peptide (GAP). We studied the effects of various known secretagogues of LHRH on the in vitro release of proLHRH fragments from the median eminence (ME) and subsequently characterized these immunoreactive products according to molecular weight (MW). GAP- and LHRH-like immunoreactive (LI) materials were secreted simultaneously into the media under basal conditions. Prostaglandin E2 stimulated release of both peptides by approximately 2-fold. Both phorbol ester and [K+] stimulated release of GAP-LI by 4-fold and LHRH-LI by 9-fold over baseline levels. When materials from [K+]-stimulated media were separated according to MW by high performance size-exclusion chromatography, a single peak eluted at 1300 MW in the same position as synthetic LHRH. Two GAP-LI peaks were observed. One eluted in the void volume, while the predominant peak co-eluted with synthetic rat GAP1-56 at approximately 6500 MW. These results indicate that GAP and LHRH are co-secreted, that they are released as intact peptides, and that activation of different intracellular pathways may cause their differential secretion. These results emphasize the importance of using both in vitro and chromatographic methodologies to evaluate the changes which may occur in LHRH prohormone processing and secretion.
Mol Cell Endocrinol 1988 Jan
PMID:Differential secretion of proLHRH fragments in response to [K+], prostaglandin E2 and C kinase activation. 328 35

Copper (Cu) and PGE2 are known to stimulate LHRH release from explants of the median eminence area (MEA) by two mechanisms distinguishable by their Ca2+ dependence. Moreover, exposure to Cu and PGE2 results in an amplified release of LHRH which is partially Ca2+ dependent, thus, resembling the release process stimulated by PGE2 alone. We have shown that LHRH release stimulated by Cu alone is Na+/Cl- dependent. By defining the Na+/Cl- dependence of PGE2- and Cu/PGE2-stimulated release of LHRH, we wished to ascertain if there is synergism between Cu and PGE2 actions. MEA of adult male rats were incubated for 5 min with 150 microM Cu and then for 15 min with 10 microM PGE2 (Cu/PGE2). Controls were incubated with Cu or PGE2. LHRH release into the medium was evaluated by RIA. Substituting Cl- in the incubation buffer with the non-permeant anion, isethionate, did not alter PGE2 stimulation of LHRH release, but it drastically inhibited Cu/PGE2 stimulation of LHRH release, indicating that this process requires a permeant monovalent anion. PGE2 and Cu/PGE2 stimulation of LHRH release were both inhibited when Na+ was substituted with Li+, or when 0.5 mM ouabain was included in the Na+-containing buffer; neither 10 microM tetrodotoxin (TTX) nor 100 microM amiloride were inhibitory. To ascertain if Na+ is required for Cu uptake, we evaluated the uptake of 67Cu by MEA explants and found that neither ouabain nor Li+ inhibited uptake, indicating that the extracellular Na+ and the activity of Na+/K+ ATPase are required for the process of LHRH release.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1988 Mar
PMID:Evidence for synergism between copper and prostaglandin E2 in stimulating the release of gonadotropin-releasing hormone from median eminence explants: Na+/Cl- requirements. 328 21

In the present study both the reverse hemolytic plaque assay for detecting luteinizing hormone (LH) secretion from single cells and LH immunocytochemistry (ICC) were applied to conduct quantitative studies on sexual differences in the gonadotrope population during postnatal development. Pituitary glands from both sexes at different ages were monodispersed with 0.1% trypsin. Freshly dispersed cells were incubated in Cunningham chambers in the presence of 10(-7) M gonadotropin-releasing hormone (GnRH) for measurement of the fraction of plaque-forming cells and the mean size of plaque formed, or attached to glass slides for measurement of the fraction of cells staining for LH by ICC. The percentage of immunostained LH cells increased with age in both sexes from about 5% of the total pituitary cell population at 5 days of age to a plateau of about 10% by 15 days and then fell to the adult level of about 5%. There were no significant sexual differences except at 30 and 40 days of age. In female rats the fraction of LH-secreting cells detected by plaque assay matched closely with that of LH-containing cells detected by ICC. However, there were significant sexual differences in the percentage of LH-secreting cells at day 15 through day 40. The mean LH output from individual cells of both sexes as indicated by the mean size of plaques also increased with age and reached a peak around 50 days. The sexual differences were first seen around 30 days of age with greater amounts in the female than in the male.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1988 May
PMID:Sexual dimorphism of pituitary gonadotropes during postnatal development in the rat. 329 58

In order to further understand the factors which influence the normal or pathologic growth of the prostate, we have characterized the receptor for epidermal growth factor (EGF) in the rat ventral prostate and have studied the hormonal regulation in this receptor. EGF binds to a single class of saturable, high affinity binding sites in total prostatic homogenate. Scatchard analysis of the binding data reveals an apparent dissociation constant (KD) of 0.93 +/- 0.08 nM and a number of sites of 4.01 +/- 0.24 fmol per mg protein. Among the peptides tested, only native EGF can displace bound [125I]EGF. Castration stimulates the concentration of prostatic EGF receptors from 25.5 +/- 3.0 to 43.4 +/- 5.4 fmol/100 mg tissue in intact and castrated animals, respectively (P less than 0.01). Treatment of castrated rats with dihydrotestosterone (DHT) inhibits the rise in prostatic EGF receptor concentration induced by orchiectomy, while estradiol, progesterone or the dopaminergic agonist CB-154, have no effect. Combined administration of DHT with the other above-mentioned steroids or CB-154 does not modify the inhibition of prostatic EGF receptor concentration induced by the androgen in castrated animals. When the data are expressed as changes in EGF receptor number in the total prostate, DHT treatment reverses the inhibitory effect induced by castration and yields an EGF binding capacity comparable to that measured in intact animals. Chronic treatment with a pure antiandrogen or a potent LHRH agonist (LHRH-A) alone has no significant effect on EGF receptor concentration in prostatic tissue, although, secondary to a reduction in prostatic weight, total prostatic EGF binding capacity is reduced following antiandrogen or LHRH-A treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1988 Mar
PMID:Androgens modulate epidermal growth factor receptor levels in the rat ventral prostate. 337 44

A quantitative electron microscopy study was carried out to characterize the luteinizing hormone (LH) contained secretory granules in response to exogenous luteinizing hormone releasing hormone (LHRH) alone or in combination with calmodulin inhibitor (W13) in orchidectomized rats pretreated with estrogen. The plasma LH concentration rose quickly 30 min after a single large LHRH injection, and then gradually increased further until 150 min. However, the rise was attenuated by supplemental administration of W13 30 min after LHRH exposure. The mean diameter of secretory granules quickly decreased inversely to the increase of plasma LH concentration after LHRH injection. However, the mean diameter increased significantly in accordance with the complete attenuation of the increase in LH release caused by administration of W13. There was an inverse correlation between the diameter of secretory granules and plasma LH concentration. Small secretory granules with low electron density frequently appeared in castration cells after LHRH injection. It is concluded that reduced size and density of secretory granules is the main morphological standard responsible for extraordinary LH secretion from gonadotrophs.
Mol Cell Endocrinol 1986 Jan
PMID:Morphological characterization of LH secretory granule response to LHRH and calmodulin inhibitor. 351 31

Degradation of LHRH and [D-Ser(tBu)6,des-Gly-NH10(2)]LHRH ethylamide (LHRH-A), during incubation with high-speed supernatants of rat testes, as assessed by reversed-phase (RP)-HPLC fractionation of the iodinated peptides and by radioimmunoassays for LHRH or LHRH-A, was principally due to a neutral 43 000 Da peptidase with apparent Km values at 25 degrees C of 0.15 microM for LHRH and 1.19 microM for LHRH-A. The peptidase was inhibited by sulphydryl reagents, TLCK, 1,10-phenanthroline, EDTA, bacitracin, other LHRH analogues, oxytocin, [Lys8]vasopressin and somatostatin. It was predomantly located in seminiferous tubule supernatants (98% of recovered activity), with much lower levels in interstitial fluid (2%), interstitial tissue or testicular particulate fractions (less than 0.8%). Extracts of cultured immature Sertoli cells produced LHRH- and LHRH-A-degradation profiles, as assessed by RP-HPLC, that were identical to those produced by testicular supernatants. Similar levels of peptidase activity/mg protein were observed in immature and adult rat testes. These studies indicate that the principal LHRH-peptidase in the rat testis is produced by cells of the seminiferous epithelium, chiefly the Sertoli cell, and may play an important role in regulating the activity of LHRH and other peptide hormones in the testis.
Mol Cell Endocrinol 1986 Jun
PMID:Degradation of luteinizing hormone-releasing hormone (LHRH) and an LHRH agonist by the rat testis. 351 17

Protein secretion by cultured pituitary cells from 14-day-old female rats was estimated using [35S]methionine incorporation followed by either one- or two-dimensional electrophoresis and autoradiography. Stimulation of total cells or gonadotrophs by LHRH promoted the synthesis and release of a specific polypeptide (apparent molecular weight 87,000, pI = 4.6). Silver staining of cellular proteins from both gonadotroph-enriched and gonadotroph-depleted populations prepared by centrifugal elutriation revealed a high concentration of this polypeptide in the gonadotrophs and a very low level in the other cell population. This species was thus called Gonadotrope Polypeptide GP-87. Release of labeled GP-87 by gonadotrophs was both time dependent (up to 4 h) and LHRH dose dependent (from 10(-9) M to 10(-7) M) as was the release of LH. Attempts to precipitate GP-87 from the incubation medium with anti-LH antiserum were unsuccessful suggesting that GP-87 is not a 'big' form of LH. TRH neither stimulated the release of GP-87 from gonadotrophs nor from lactotrophs though it did stimulated PRL release. From these data, we conclude that gonadotrophs in culture synthesize a specific polypeptide (GP-87), LHRH stimulates both the synthesis and release of GP-87, and the pituitary cell response is peptide specific. The LHRH-induced synthesis and release of GP-87 could be an important step in the molecular processes that regulate gonadotrophin secretion.
Mol Cell Endocrinol 1986 Jul
PMID:LHRH promotes the synthesis and release of a 87,000 Da protein (GP-87) by enriched gonadotrophs. 352 13

Micropipettes were used to record electrical activity from single neurons in hypothalamic tissue slices, in the hypothalamic arcuate nucleus (ARC), and in the periventricular and suprachiasmatic preoptic nuclei (POA). Responses were measured following in vitro application of luteinizing hormone releasing hormone (LHRH), and two analogues: LHRH models 1 and 3. Model 1 (pyroGlu-His-Trp-Ser-Phe-Thr-Ile-Lys-Ile-ThrNH2) had amino acid substitutions in residues 5-10 designed to form an amphiphilic beta-strand structure. Model 3 (pyroGlu-His-Trp-Ser-Phe-Gly-Ile-Lys-Pro-SerNH2) was also designed to possess amphiphilic characteristics, but also more closely to resemble the native peptide. Electrical recording results showed that LHRH was able both to excite or inhibit different hypothalamic neurons, and that it was more effective in the preoptic area than in the arcuate nucleus. Responses to LHRH model 3 were strongly correlated with responses to LHRH, in their occurrence and their direction, for both of the brain regions studied. Moreover, LHRH models 1 and 3 also retained the neuromodulatory effects of LHRH on cellular responses to norepinephrine and serotonin. Thus, LHRH analogues, designed to possess an amphiphilic beta-structure, preserved some of the properties of LHRH when tested electrophysiologically in the central nervous system.
Mol Cell Endocrinol 1986 Dec
PMID:Electrophysiological test of an amphiphilic beta-structure in LHRH action. 354 30


<< Previous 1 2 3 4 5 6 7 8 9 10