Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human seminal plasma obtained by centrifugation of human semen contains a factor capable of selectively inhibiting the secretion of FSH both in vivo (reduction of the levels of FSH in rats 24 h after castration) and in vitro (reduction of the FSH released by LH-RH in rat pituitary cell culture). This effect is not due to testosterone, oestradiol-17 beta or progesterone present in the active fractions. The factor has the characteristics of a protein in that its biological activity is destroyed by heat and trypsin digestion. It does not resemble androgen-binding protein. The biological action is not completely specific for FSH as inhibition of LH can be seen with doses usually higher than those which produce inhibition of FSH alone. There is no effect on TSH or prolactin levels in vitro. The factor clearly acts on the release and synthesis of gonadotrophins by gonadotrophs but an effect on the hypothalamus is not excluded. This factor fits the definition of inhibin.
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PMID:Identification in human seminal fluid of an inhibin-like factor which selectively regulates FSH secretion. 29 6

This communication presents evidence for the existence in the ovine testis of proteinaceous factors which suppress LH as well as FSH. Isolation of these factors has been achieved by using three different procedures: cytosol preparation, metaphosphoric acid extraction and ultrafiltration. Chromatography of cytosol or metaphosphoric acid extract on Sephadex G-75 resulted in separation into three protein fractions designated as G-75-I, II and III in order of their elution. When administered to castrated male rats, Fraction G-75-I suppressed circulatory levels of LH (53% inhibition, P less than 0.05) without altering FSH. The most retarded fraction, G-75-III, suppressed FSH (29% inhibition, P less than 0.001) without any concomitant change in LH. When fraction G-75-III was further fractionated on Sephadex G-25, three components were found and two, G-25-II and G-25-III, were biologically active. These fractions were homogeneous on polyacrylamide disc-gel electrophoresis. The FSH-suppressing factor (inhibin) was heat labile and susceptible to trypsin digestion, indicating that it is proteinaceous. Treatment with urea did not reveal any subunits. The molecular weight of this factor, as determined by gel filtration and SDS-urea gel electrophoresis was estimated to be around 1400-1500. The absence of sialic acid and the molecular weight data suggested that the isolated material was a simple protein and probably a small peptide. Gel filtration on Sephadex G-75 of the metaphosphoric acid extracts of liver, kidney, testis and ovary revealed an identical elution pattern for ovarian and testicular inhibin.
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PMID:Characterization of a gonadal factor involved in the control of FSH secretion. 29 12

In 2 adult male patients with 49 chromosomes, an XXXXY sex chromosome constitution was confirmed by trypsin-Giemsa banding sites. Clinical findings as well as fingerprint ridge counts were typical of the syndrome. Primary hypogonadism was documented by finding low serum testosterone and raised serum LH and FSH levels. Several radiological abnormalities, not previously described in this syndrome, were seen in 1 patient.
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PMID:Chromosome banding studies in two patients with XXXXY syndrome. 56 65

Prolactin binding sites have been reported in a variety of tissues that are hormonally responsive to prolactin (PRL). A synergistic effect of PRL and androgens upon the secondary sexual structures of the male rat has been demonstrated. The present study was designed to: 1) determine if there are PRL binding sites in a membrane-rich particulate fraction of the rat ventral prostate: and 2) study the effect of changing the hormonal environment upon this specific PRL binding. The binding of lactoperoxidase iodinated ovine prolactin (I125-PRL) to rat prostatic membrane preparations was assayed by the method of Shiu and Friesen. Serum LH and PRL were measured by radioimmunoassay. The specific binding of I125-PRL that was observed in the prostatic membrane preparation of intact adult male rats was readily displaced by excess unlabelled ovine or rat PRL but not by rat LH or FSH. This binding was decreased by heating or trypsin treatment of the membrane preparation. Tissue specificity was demonstrated in that no specific binding was observed in membrane preparations of lung or spleen from these male rats. Prostatic membrane preparations from adult rats that were castrated for either 4 or 8 days showed a 90% decrease in specific I125-PRL binding while serum PRL values were not changed. Daily subcutaneous administration of testosterone propionate (2.0 mg/rat) to 4-day castrated adult rats resulted in I125-PRL binding comparable to that of intact rats. The data show that a reduction of endogenous androgens results in diminished I125-PRL binding in the ventral prostate of the rat.
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PMID:Prolactin binding in the rat ventral prostate. 81 36

The synthesis and secretion of trypsin (trypsin model serine protease) inhibitors are regulated in ovarian follicles by gonadotropins. The superovulation stimulations with 400 IU FSH, 1000 IU PMSG, 1000 IU HCG, 750 IIU PMSG + 750 IU HCG influence in a different way the trypsin inhibiting activities (TIA) of blood plasma (BP) (Figs 1 and 2) and follicular fluid (fig. 3); this points to a possibility of local effects. An increase in the average values of TIA in BP was statistically significant during the whole experiment: P less than 0.05 to P less than 0.001 (following the administration of PMSG+HCG, or PMSG, and HCG); Antisergon administered in 68 hours after PMSG reduced this increase. The changes in the fraction of low-molecular TIA in BP (after BP treatment with perchloric acid) were of converse nature; a decrease in the average values ranged from P less than 0.02 to P less than 0.001 (following PMSG or other stimulations). Antisergon did not influence this decrease. The changes observed on particular days of the trial (Figs. 1 and 2) also indicate different effects of the preparations, mainly of the component LH, which resulted in the occurrence of large nonovulating follicles (greater than 10 mm--"cystic" ones). No such follicles were observed in nonstimulated ewes and after FSH stimulation. The administration of antisergon (goat's antiserum against PMSG) 68 hours after PMSG administration did not prevent their creation. The TIA of follicular fluid (FF) of antral follicles was on average tenfold in comparison with that of blood plasma; and the TIA FF of follicles greater than 10 mm was higher (up to P less than 0.001) than the TIA FF of follicles less than 10 mm. The administration of Antisergon in shorter intervals following PMSG administration (12, 24, 48 and 58 hours) influenced the average values of TIA BP in 120 hours (since PMSG administration) in dependence on time (Tab. I). The effects of Antisergon administered in 12 and 24 hours after PMSG administration on the TIA BP were insignificant if it was administered in 48 and 58 hours the TIA BP increased (P less than 0.02; P less than 0.001) in comparison with the interval of 12 hours. The TIA FF of follicles less than 5 mm, 5-10 mm and greater than 10 mm varied in dependence on the time intervals of Antisergon administration (Fig. 4). The statistical significance of these changes in shown in Tab. II.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[The anti-proteolytic activity of blood and ovarian follicular fluid in sheep after stimulation with serum gonadotropin (PMSG) and administration of Antisergon]. 182 Oct 81

We have examined the effects of Sertoli cell-secreted proteins (SCSP) on [3H]thymidine incorporation by purified preparations (greater than 96%) of rat Leydig cells to determine whether Sertoli cells influence DNA synthesis in these cells in vitro. Incubation of Leydig cells isolated from testes of rats of ages 16 to 90 days with SCSP (Mr greater than 10,000) induced significant dose-, time- and age-related increases in [3H]thymidine incorporation by the cells. A dose-response curve to SCSP showed that as little as 0.2 micrograms SCSP/ml consistently induced a small but significant increase (31% and 10% above control; P less than 0.001) in [3H]thymidine incorporation by Leydig cells isolated from immature (26 days) and mature (70 days) rats, respectively. The maximum response (230% and 48% above control) was obtained with a concentration of 18 micrograms SCSP/ml in cells isolated from immature and mature rats, respectively. Hydroxyurea, a specific inhibitor of replicative DNA synthesis, significantly (P less than 0.001) inhibited both basal and SCSP-induced [3H]thymidine incorporation in Leydig cells from immature and adult rats without affecting the viability of the cells. Incubation of immature rat Leydig cells in SCSP for 48 h also stimulated a 3-fold increase in cell number. The component of the crude SCSP which stimulated Leydig cell [3H]thymidine incorporation is trypsin-sensitive, heat-stable, and adsorbs to a heparin-agarose affinity column but not to concanavalin A-Sepharose. The secretion of this factor(s) by Sertoli cells is stimulated independently by FSH and testosterone. These results demonstrate for the first time that cultured Sertoli cells secrete a protein(s) which, in vitro, stimulates rat Leydig cell replicative DNA synthesis.
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PMID:Sertoli cell-secreted protein(s) stimulates DNA synthesis in purified rat Leydig cells in vitro. 223 58

Animals with impaired immune function show numerous reproductive disorders. To determine whether immune factors might play a direct role in the regulation of ovarian function, we examined the effects of Concanavalin-A-stimulated lymphocyte supernates (CAS) on steroidogenesis by cultured rat granulosa cells. Granulosa cells from immature estrogen-primed rats were incubated for 48 h with increasing doses of CAS in the presence or absence of FSH. In the absence of FSH, CAS produced a dose-dependent increase in progestin (progesterone and 20 alpha-hydroxyprogesterone) production to a maximum of 190-fold greater than untreated controls, but did not stimulate estrogen production. In the presence of FSH, the stimulatory effect of CAS on progestin production was additive with that of FSH. In contrast, CAS inhibited FSH-stimulated estrogen production in a dose-dependent manner. The maximum inhibition was greater than 90%. Addition of the phosphodiesterase inhibitor isobutylmethylxanthine to CAS-containing cultures significantly enhanced the stimulatory effect of CAS on progesterone production, suggesting that this action may be exerted through a cAMP-mediated pathway. The stimulatory component of CAS was heat labile, acid stable, and required a trypsin-sensitive cell surface recognition site, whereas the inhibitory component was both heat and acid stable. Neither the stimulatory nor the inhibitory actions of CAS were mimicked by treating granulosa cells with supernates from Concanavalin-A-stimulated neonatal cardiac or hepatic cell cultures. Thus, the present studies demonstrate that secretory products of lymphocytes (collectively termed lymphokines) can affect steroidogenesis in cultured rat granulosa cells. These data imply that immune cell factors may play a significant role in the differentiation and maturation of granulosa cells.
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PMID:Lymphokines from concanavalin-A-stimulated lymphocytes regulate rat granulosa cell steroidogenesis in vitro. 245 14

Sertoli cell-enriched cultures isolated from immature rat testes by enzymic treatments were investigated by intracellular microelectrode recordings. The hyperpolarization of cells induced by FSH was independent of the age of the rats (7-37 days) and was unchanged by exposure to a hormone-free medium or to a glycine buffer of pH 3. It was reduced by treatments which decreased the electrical coupling between cells either by an increase of intracellular calcium [i.e. calcium ionophore (A 23187, 5 x 10(-6) M), general anaesthetic (heptanol, 3.5 mM) and uncoupler of oxidative phosphorylations (carbonylcyanide m-chlorophenylhydrazone-CCmP, 10(-6) M)] or by a decrease of extracellular calcium [i.e. 0Ca + EGTA (1 mM) medium]. These effects were partly or totally reversed by a recovery period in a drug-free medium. Similar results were obtained by an exposure to trypsin (0.05%) followed by a second mechanical dispersion, but new cell hyperpolarization was induced by a new exposure to FSH. This electrophysiological study suggests an initial effect of FSH on the junctional complex between Sertoli cells, then the control by calcium of this complex.
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PMID:Effect of uncoupling treatments on FSH-induced hyperpolarization of immature rat Sertoli cells from Sertoli cell-enriched cultures. 249 56

The effects of FSH and testosterone on inhibin mRNA expression and inhibin production by highly purified Sertoli cell preparations were examined. Sertoli cells were isolated from testes of 22-day-old rats by sequential trypsin, collagenase and hyaluronidase treatments, with subsequent osmotic shock treatment on day 3 of culture. Contamination by peritubular and germ cells was less than 0.5 and 1-3% respectively. Intracellular and secreted inhibin levels were measured by radioimmunoassay, using Sertoli cells which were incubated for 24 h in the absence or presence of FSH and testosterone from days 4 to 5 of culture. FSH stimulated the cellular inhibin content and the secreted inhibin level by four- and sevenfold respectively, with a half-maximal effective dose of 5-50 ng/ml. Under the present incubation conditions, testosterone (1 mumol/l) had no effect on immunoreactive inhibin levels in either the presence or absence of FSH. Similarly, the expression of inhibin alpha-subunit mRNA was increased following FSH stimulation, whereas testosterone had no effect. The expression of inhibin beta B-subunit mRNAs was not influenced by FSH or testosterone. It is concluded that highly purified Sertoli cell preparations, with a very low number of peritubular or germ cells, are fully responsive to FSH with respect to inhibin mRNA expression and inhibin production.
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PMID:Effects of FSH and testosterone on highly purified rat Sertoli cells: inhibin alpha-subunit mRNA expression and inhibin secretion are enhanced by FSH but not by testosterone. 250 18

Testicular peritubular cells produce paracrine mediators which modulate Sertoli cell function. The production of these mediators (P Mod-S) is controlled by androgens suggesting that mesenchymal-epithelial interactions play an important role in androgen action in the testis. We investigated whether mesenchymal cells from the prostate, another androgen target tissue, produce analogous mediators. To this end rat Sertoli cell cultures were exposed to dialyzed spent media derived from testicular peritubular cells, prostatic stromal cells or footsole fibroblasts. It is demonstrated that the effects of spent media from peritubular cells and stromal cells are nearly identical: they stimulate the production of androgen binding protein and transferrin and they inhibit FSH-inducible aromatase activity. The active principle (or principles) involved is non-dialyzable, heat sensitive and trypsin sensitive. Its production is markedly stimulated by androgens. Fibroblast spent media are inactive. It is concluded that mesenchymal tissue derived from different androgen target tissues may produce identical or similar mediators of androgen action acting on epithelial cells.
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PMID:Stromal cells from the rat prostate secrete androgen-regulated factors which modulate Sertoli cell function. 274 20


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