Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of follicle-stimulating hormone (FSH) and cyclic guanosine 3',5'-monophosphate (cGMP) on spontaneous oocyte maturation and cyclic adenosine 3',5'-cumulus-monophosphate phosphodiesterase activity (cAMP-PDE) were evaluated by using cumulus-oocyte complexes (COCs) from proestrous hamsters. After a 2-h incubation period, FSH (10 micrograms/ml and 1 microgram/ml) reduced the percentage of maturing oocytes compared with controls. This inhibition was partially overcome when cGMP-elevating agents (8-Bromo-cGMP, atrial natriuretic factor or sodium nitroprusside) were included with FSH. After a 3-h period, incubation with FSH and cGMP-elevating agents alone increased the maturation rate above that of the controls. The accelerating effects of cGMP on the maturation rate appear to be caused by its capacity to lower cAMP levels. Combining FSH (1 microgram/ml) with sodium nitroprusside reduced cAMP levels in COCs (not oocytes) compared with groups exposed to FSH alone. FSH increased cGMP levels in COCs in a dose- and time-dependent manner. Both FSH and cGMP-elevating agents produced a dose-dependent increased cAMP-PDE activity in COCs (not oocytes) following a 2-h incubation period. Together, these results suggest that, in vivo, FSH stimulates a rise in both cAMP and cGMP in COCs. While the increase in cAMP may be the initial meiotic trigger, cGMP may serve to subsequently lower cAMP by activating cAMP-PDE and thus permit the maturational process to continue.
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PMID:The effects of follicle-stimulating hormone and cyclic guanosine 3',5'-monophosphate on cyclic adenosine 3',5'-monophosphate-phosphodiesterase and resumption of meiosis in hamster cumulus-oocyte complexes. 285 23

Pre-incubation of rat Sertoli cells with concentrations of follicle-stimulating hormone (FSH) too low to stimulate plasminogen activator (PA) secretion, provoked an inhibition of its subsequent stimulation by an effective dose of the hormone. A kinetic study of this desensitization was performed using equine FSH (which exhibits prolonged stimulation of PA secretion) and porcine FSH (which like all other FSH tested, provokes a transient response). Low non-stimulating concentrations of both hormones were shown to inhibit the subsequent PA response to each of them. Desensitization of rat Sertoli cells by low (non-stimulating) concentrations of FSH did not modify the typical time course (transient or prolonged) of PA secretion under subsequent stimulation by porcine or equine FSH, respectively. Only the intensity of the response to each hormone was dramatically reduced. Besides, the induction of desensitization by these non-stimulating concentrations of FSH was shown to be very rapid (10-15 min). The precise mechanism of this desensitization is not yet clear but its abolishment by the cyclic nucleotide phosphodiesterase (PDE) inhibitor MIX is consistent with the hypothesis that activation of PDE occurs at lower FSH concentration than adenylate cyclase activation.
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PMID:Homologous desensitization of rat Sertoli cells by non-stimulating concentrations of follicle-stimulating hormone. 295 41

Vasoactive intestinal peptide (VIP) and VIPergic nerve fibers are present in the ovaries of several mammalian species, suggesting a possible ovarian action of VIP. We have investigated the direct effects of synthetic porcine VIP on rat granulosa cell steroidogenesis in vitro. The cells were obtained from immature, hypophysectomized, estrogen-primed rats, and cultured in a serum-free medium for 24 h in the absence or presence of varying amounts of VIP. Medium steroids were then determined by specific radioimmunoassay. Vasoactive intestinal peptide dose-dependently stimulated progesterone, 20 alpha-hydroxypregn-4-ene-3-one (20 alpha-OH-progesterone), and estrogen production with an approximate ED50 value of 3 X 10(-8) M. Maximum steroid production induced by VIP ranged from 15% to 28% of that seen with maximal follicle-stimulating hormone (FSH) stimulation. In contrast to the ability of FSH to induce luteinizing hormone (LH) receptor formation, treatment with VIP did not increase [125I]iodo-human chorionic gonadotropin (hCG) binding to granulosa cells. The ability of several gastrointestinal peptides, having 17-44% sequence identity to VIP, to stimulate granulosa cell steroidogenesis was also tested. The most closely related peptide, PHM-27 was less effective than VIP, and the least closely related, secretin and glucagon, were ineffective at 10(-6) M. Vasoactive intestinal peptide seems to act at least partly through cyclic 3',5'-adenosine monophosphate (cAMP)-dependent processes: addition of a phosphodiesterase inhibitor significantly potentiated the VIP stimulation of granulosa cell steroidogenesis, and VIP was capable of producing a dose- and time-dependent increase in both intracellular and medium cAMP levels. Vasoactive intestinal peptide stimulation of estrogen production seemed to be a result of increased aromatase activity. The increased progesterone production was associated with increased pregnenolone production, increased rate of conversion of pregnenolone to progesterone via 3 beta-hydroxysteroid dehydrogenase, and decreased metabolism of progesterone via 20 alpha-hydroxysteroid dehydrogenase. These results indicate that VIP exerts a specific action on granulosa cells to increase estrogen and progestin production. The observed direct effects of VIP, coupled with its identification in the ovary, suggest that VIP may be a physiologically important regulator of ovarian activity.
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PMID:Vasoactive intestinal peptide: a novel stimulator of steroidogenesis by cultured rat granulosa cells. 299 97

The ovarian granulosa cell has recently been shown to be the site of Somatomedin C (Sm-C) production, reception, and action. To further elucidate the relevance of Sm-C to granulosa cell physiology, we have undertaken to study the regulation of its receptor under in vitro conditions using a primary culture of rat granulosa cells. Granulosa cells cultured without treatment for 72 h displayed limited, albeit measurable, specific Sm-C binding. However, continuous treatment with increasing concentrations of follicle-stimulating hormone (FSH) for the duration of the 72-h incubation period resulted in dose-dependent increments in Sm-C binding (1.7-, 2.9-, 3.9-, and 3.6-fold increases over untreated controls for 50, 100, 180, and 330 ng/ml of FSH, respectively). This apparent up regulatory action of FSH proved time-dependent, with a minimal time requirement of 24-48 h. Granulosa cell Sm-C binding was similarly enhanced following elevation of the intracellular cAMP content by a series of cAMP-generating agonists, inhibition of cAMP-phosphodiesterase activity, or the provision of nondegradable cAMP analogs. Our findings further indicate that high dose forskolin, like FSH, is capable of augmenting Sm-C binding by itself, that a relatively inactive low dose of forskolin synergizes with FSH in this regard, but that combined treatment with maximal stimulatory doses of both agonists does not prove additive. Taken together, these observations indicate that FSH is capable of exerting a stimulatory effect on granulosa cell Sm-C binding and that cAMP, its purported intracellular second messenger, may play an intermediary role in this regard.
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PMID:Follicle-stimulating hormone enhances somatomedin C binding to cultured rat granulosa cells. Evidence for cAMP dependence. 300 11

We have previously shown that equine follicle-stimulating hormone (FSH) stimulates plasminogen activator secretion in Sertoli cells at much lower concentrations than would be expected from its relative binding activity. We have introduced the term 'superactivity' to designate this particular behavior. In the present study, we show that equine FSH triggers a long-lasting (20 h) plasminogen activator secretion, whereas rat, porcine and ovine FSH as well as equine LH and equine choriogonadotropin (CG) provoke a short-term response (2.5 h). Moreover, equine FSH was also shown to be superactive in the stimulation of estradiol secretion and cyclic AMP production. This indicates that the step responsible for the long-term stimulation by equine FSH is not located beyond cAMP accumulation. Equine and porcine FSH were found to be equally stable during incubation with the cells demonstrating that equine FSH superactivity was not due to higher stability. Besides, phosphodiesterase inhibition led to a similar increase in the responses to both hormones. This rules out the possibility that equine FSH superactivity is due to less stimulation of phosphodiesterase activity. All these data strongly suggest that equine FSH exhibits superactivity in rat Sertoli cells by stimulating adenylate cyclase activity for a much longer period of time than do all other gonadotropins. The molecular mechanism of this outstanding behavior remains to be elucidated.
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PMID:Study of the superactivity of equine follicle-stimulating hormone in in vitro stimulation of rat Sertoli cells. 301 21

A sensitive in vitro bioassay for measuring serum follicle-stimulating hormone (FSH) levels has been developed based on the stimulation of estrogen production by cultured rat granulosa cells. In the presence of androstenedione, FSH stimulated estrogen production in a dose-dependent manner. Cell sensitivity to FSH was further enhanced by the addition of diethylstilbestrol, a phosphodiesterase inhibitor, insulin, and human chorionic gonadotropin. Although the inclusion of 4% gonadotropin-free serum from hypophysectomized rats inhibited granulosa cell responsiveness, pretreatment of serum with polyethylene glycol (12%) substantially eliminated the serum interfering effect without loss of FSH activity. In normal male and female rats, serum bioactive FSH levels were low, while castration increased these levels 2.6-and 5.7-fold, respectively. These increases were suppressed by treatment with testosterone propionate or estradiol benzoate. This in vitro assay allows the measurement of circulating bioactive FSH and provides a convenient tool to advance studies on the role of FSH in the neuroendocrine control of gonadal maturation and reproductive cycles.
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PMID:Sensitive in vitro bioassay for the measurement of serum follicle-stimulating hormone. 393 96

Epinephrine, norepinephrine, and isoproterenol produced dose-dependent stimulation of ornithine decarboxylase (EC 4.1.1.17) activity in isolated porcine granulosa cells maintained under defined conditions in vitro. beta- but not alpha-receptor-blocking agents prevented enzyme stimulation by catecholamines. Application of preferential beta-1 and beta-2-receptor antagonists and agonists localized the epinephrine effect to beta-2-adrenergic mediation. Epinephrine action was enhanced by the phosphodiesterase inhibitor, 1-methyl-3-isobutyl-xanthine, but not by saturating concentrations of the cyclic AMP analogue, 8-bromocyclic AMP, of follicle-stimulating hormone, or of prostaglandin E2. However, stimulation by epinephrine was additive to that of luteinizing hormone. Follicular fluid obtained from immature Graafian follicles contained concentrations of norepinephrine and epinephrine active in vitro. Thus, catecholamines may participate in the regulation of ornithine decarboxylase activity in the ovary. Catecholamine effects may be mediated by beta-2-receptors linked to the adenylate cyclase system.
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PMID:Beta-2-Adrenergic stimulation of ornithine decarboxylase activity in porcine granulosa cells in vitro. 615 44

Sertoli cells in primary cultures produce plasminogen activator activity, and release it into the medium at rates greatly influenced by a variety of factors, including cell density, the presence of hormones, incubation temperature and duration of culture. In Sertoli cells maintained in culture in the presence of dibutyryl cAMP, the amounts of plasminogen activator activity secreted per cells were maximal at cell densities up to 2.5 microgram DNA/cm2 (350 units/microgram cell DNA), and declined to 40 units/microgran cell DNA at a density of 22 micrograms DNA/cm2. Concentrations of follicle-stimulating hormone (FSH) required to elicit half-maximal stimulation of the production of plasminogen activator activity were 0.37 micrograms/ml for oFSH-NIH S12 and 8 ng/ml for the more purified of SH-S1528C2. The ED50 for dibutyryl cAMP was found to be 0.08 mM. Addition of an inhibitor of phosphodiesterase (3-isobutyl-l-methylxanthine) enhanced the formation of plasminogen activator by cells cultured in the presence of FSH. Addition to the culture medium of testosterone, epidermal growth factor, insulin, human chorionic gonadotropin or prostaglandins (E1, E2 or F1 alpha) did not result in increased production of PA activity by Sertoli cells. Cells in culture for as long as 14 days remained responsive to FSH or dibutyryl cAMP. Increases in cellular levels of plasminogen activator became evident within 2-4 after addition of either FSH or dibutyryl cAMP to the medium. The stimulation of FSH or dibutyryl cAMP of the production of plasminogen activator activity was shown to be dependent upon de novo synthesis of RNA and protein. Levels of enzyme activity released by Sertoli cells maintained in culture for 48 h at 37 degrees C were approx. 50% higher than plasminogen activator released by cells cultured at 32 degrees C. The control of the production of plasminogen activator activity by Sertoli cells was discussed in relation to the control of plasminogen activator production by granulose cells, and the possible role of plasminogen activator in gonadal functions.
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PMID:The control of the synthesis and secretion of plasminogen activator by rat sertoli cells in culture. 617 77

Granulosa cells from small (1-2 mm) follicles of porcine ovaries produced cAMP in response to follicle-stimulating hormone (FSH); they produced little cAMP in response to human chorionic gonadotropin (hCG) or to cholera toxin. Production, estimated by quantification of total cAMP (medium + cells) by radioimmunoassay, appeared to be episodic in the absence or presence of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine (MIX) and continued for at least 20 h. Results of dual incubation experiments with thorough washing of cells between incubations indicated that cells remained responsive to FSH, to hCG, and to cholera toxin after prior exposure to homologous stimulator. Preincubation of cells for 3 h in the absence of stimulator enhanced FSH responsiveness. In experiments with heterologous stimulators in two incubations, first, preincubation with FSH enhanced subsequent hCG and cholera toxin responsiveness; and second, preincubation with hCG or cholera toxin did not affect FSH responsiveness. Desensitization of FSH-activated adenylate cyclase was never greater than 35%; the degree of attenuation was dependent on FSH concentration and duration of exposure to FSH. Cells perifused with medium containing MIX and a maximally effective concentration of FSH for 5 h released cAMP continuously. In summary, the results indicated that porcine granulosa cells do not become unresponsive to FSH after prolonged exposure to FSH in vitro.
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PMID:Porcine granulosa cell desensitization: prolonged FSH-responsive cAMP production in vitro. 618 6

The antigonadal effects of gonadotropin-releasing hormone in ovarian granulosa cells are due to attenuation of the adenosine 3',5'-monophosphate (cyclic AMP) response to follicle-stimulating hormone. Agonists of gonadotropin-releasing hormone progressively inhibit adenylate cyclase and stimulate phosphodiesterase activities in cultured granulosa cells, indicating that blockade of gonadotropin action is attributable to the combined effects of decreased production and increased degradation of cyclic AMP.
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PMID:Gonadotropin-releasing hormone: regulation of adenosine 3',5'-monophosphate in ovarian granulosa cells. 627 16


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