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:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenylate cyclase activity in particulate preparations of ovarian tumors from 47 women was determined by measuring the conversion of phosphorus 32-labeled adenosine triphosphate to phosphorus 32-labeled cyclic adenosine monophosphate. Ovarian cancers typically exhibited an active adenylate cyclase which was stimulated by 50 mumol/L 5'-guanylylimidodiphosphate and 10 mmol/L of sodium fluoride. This activity was comparable to that in particulates of normal postmenopausal ovaries and was independent of the class of tumor. There was no significant increase in adenylate cyclase activity in any epithelial or germinal tumor in the presence of either 250 nmol/L of human chorionic gonadotropin or 333 nmol/L human follicle-stimulating hormone. However, cyclic adenosine monophosphate production by two sex cord stromal tumors was stimulated by follicle-stimulating hormone, but not by human chorionic gonadotropin. Follicle-stimulating hormone stimulated a threefold increase in activity in the granulosa-theca cell tumor, with an activation constant (57 nmol/L) similar to that in follicle-stimulating hormone-responsive rat ovaries. Prostaglandin E1 (50 mumol/L) increased cyclic adenosine monophosphate production by epithelial tumors more than twofold. These data suggest that sex cord stromal tumors, unlike the more common epithelial tumors, can be modulated directly by gonadotropin.
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PMID:Adenylate cyclase in human ovarian cancers: sensitivity to gonadotropins and nonhormonal activators. 300 Jan 83

The induction of granulosa cell differentiation by follicle-stimulating hormone (FSH) is characterized by cellular aggregation, expression of luteinizing hormone (LH) receptors, and biosynthesis of steroidogenic enzymes. These actions of FSH are mediated by activation of adenylate cyclase and cAMP-dependent protein kinase and can be mimicked by choleragen, forskolin, and cAMP analogs. Gonadotropin releasing hormone (GnRH) agonists inhibit these maturation responses in a calcium-dependent manner and promote phosphoinositide turnover. The phorbol ester phorbol 12-myristate 13-acetate (PMA) also prevented FSH-induced cell aggregation and suppressed cAMP formation, LH receptor expression, and progesterone production, with an ID50 of 0.2 nM. In FSH-treated cells, PMA did not reduce the initial increase in cAMP formation during the first 24 hr of culture but prevented its secondary increase from 24 to 48 hr. PMA also inhibited LH receptor induction by cholera toxin, forskolin, and 8-bromo-cAMP, but it did not impair cAMP responses to the former two agents, indicating that the site of action of the phorbol ester is distal to adenylate cyclase. The early stimulation of cAMP-dependent protein kinase activity by FSH was also unaffected by PMA, consistent with its lack of effect on the initial cAMP response to FSH. However, PMA caused a marked decrease in cytosolic protein kinase C activity within 1 min of its addition to the cells. The permeant diacylglycerols, 1-oleoyl-2-acetoyl-sn-glycerol and sn-1,2-dioctanoyl glycerol, also inhibited LH receptor formation, while the nonpermeant diacylglycerol, diolein, was inactive. These results indicate that in situ activation of protein kinase C by PMA or permeant diacylglycerols inhibits cAMP-dependent granulosa cell differentiation, and suggest that the inhibitory actions of GnRH agonists on granulosa cell maturation are also mediated by protein kinase C.
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PMID:Inhibition of gonadotropin-induced granulosa cell differentiation by activation of protein kinase C. 300 7

It is proposed that premenstrual syndrome results from the action of elevated gonadotropin levels in various tissues of body other than their natural target organs. These levels are derived from an increased sensitivity to estrogen after pregnancy, childbirth, etc., particularly with respect to the positive feedback on gonadotropin release from the pituitary. Estrogen in conjunction with gonadotropin-releasing hormone (GnRH) releases excessive amounts of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) at ovulation and in the premenstrual phase (post-menopausal patients have greatly elevated gonadotropins and can also demonstrate cyclic symptoms). Gonadotropin action via adenylate cyclase in the adrenal cortex elevates cortisol, while antagonism of parathyroid hormone action on bone gives rise to hypocalcemia. The physiological and psychological symptoms may thereby be explained.
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PMID:Pre-menstrual syndrome--are gonadotropins the cause of the condition? 300 49

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

An in vitro superfusion system was used in an attempt to identify the cellular systems involved in the Ca2+ dependence of gonadotropin-releasing hormone (GnRH) actions in the frog, Rana pipiens. Superfusion with 5 microM A23187 (a calcium ionophore) or phorbol myristate acetate (an analog of diacylglycerides) caused marked increases in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Exclusion of Ca2+ from the medium prevented the stimulatory effects of PMA. The potent stimulator of adenylate cyclase, forskolin, caused only slight stimulation of LH and FSH secretion, which was also prevented by removal of Ca2+. The cytoskeletal disruptive agents colchicine, nocodazole, and cytochalasin B, and the calmodulin inhibitors, trifluoperazine and pimozide, had no significant effects on the action of GnRH. Overall, these results indicate that the major mechanisms of Ca2+ involvement in the response to GnRH by the frog pituitary are similar to that of mammals, with the possible exceptions of lesser roles for calmodulin and the cytoskeleton in the frog. The study suggests that polyphosphatidyl-inositol-diacylglyceride metabolism may be critical in understanding the mechanism of GnRH action in frogs.
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PMID:The cellular basis of the calcium dependence of GnRH-stimulated gonadotropin release from frog, Rana pipiens, pituitaries. 309 96

Protease inhibitors are known to suppress basal, fluoride-, and hormone-stimulated adenylate cyclase activities. The thrombin inhibitor, dansyl-arginyl-(4'-ethyl)piperidine amide (DAPA), also specifically inhibits the binding of gonadotropins to their receptors. Our studies were undertaken to find a concentration of DAPA that would specifically inhibit gonadotropin-stimulated adenylate cyclase without significantly altering basal, fluoride-, isoproterenol-, or prostaglandin E1-stimulated cyclase. Basal adenylate cyclase activity was not inhibited by DAPA in either human chorionic gonadotropin (hCG)- or follicle-stimulating hormone (FSH)-responsive rat ovarian plasma membranes. Human chorionic gonadotropin-stimulated cyclase was completely inhibited by DAPA at a concentration of 2.96 mM; the ID50 was 1.32 mM. Follicle-stimulating hormone-stimulated cyclase was completely inhibited by a DAPA concentration of 4.44 mM, and the ID50 was 1.75 mM. Dansyl-arginyl-(4'-ethyl)piperidine amide (2.96 mM) inhibited isoproterenol-, prostaglandin E1-, and fluoride-stimulated cyclase in hCG-responsive membranes by 11%, 28%, and 35%, respectively. Dansyl-arginyl-(4'-ethyl)piperidine amide (4.44 mM) inhibited fluoride- and prostaglandin-stimulated cyclase in FSH-responsive membranes by 10% and 11%, respectively. The data show that appropriate concentrations of DAPA can antagonize gonadotropin-stimulated adenylate cyclase while only minimally affecting fluoride- and other receptor-activated cyclase activities.
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PMID:Inhibition of gonadotropin-stimulated adenylate cyclase by dansyl-arginyl-(4'-ethyl)piperidine amide (DAPA). 310 59

Recombinant human interleukin-1 (IL-1) inhibits the follicle-stimulating hormone (FSH)-induced development of luteinizing hormone (LH) receptors and suppresses progesterone secretion in cultured rat granulosa cells. Since activation of adenylate cyclase by FSH is considered to be the primary second messenger system responsible for differentiation of granulosa cells, we examined whether IL-1 could alter the FSH, cholera toxin, or forskolin-induced accumulation of cyclic adenosine 3', 5'-monophosphate (cAMP) from these cells. In addition, we sought to determine if IL-1 could influence differentiation induced by the cAMP analog, 8-bromo cAMP. Cells collected from ovaries of immature, diethylstilbestrol-treated rats were stimulated to differentiate by addition of FSH, cholera toxin, forskolin, or 8-bromo cAMP to the cultures. IL-1 or interleukin-2 (IL-2) was added to some of the tubes, and the primary cultures were incubated for various periods of time. At the end of the culture, the tubes were centrifuged, the medium was saved for progesterone and cAMP radioimmunoassay, and the cells were assayed for specific 125I-human chorionic gonadotropin (hCG) binding to determine the number of LH receptors. In the presence of FSH, IL-1, at a dose as small as 5 ng/ml, but not IL-2, significantly inhibited LH receptor formation and suppressed progesterone secretion in a dose-related manner. IL-1 also significantly suppressed FSH-induced cAMP accumulation after 72 h of incubation but did not appear to do so in a dose-related fashion. In the presence of FSH, IL-1 did not significantly alter the protein content of granulosa cells at the end of culture. During stimulation of granulosa cells with cholera toxin, forskolin, or 8-bromo cAMP, IL-1 significantly reduced LH receptor formation compared to that observed in the absence of IL-1. However, in contrast to IL-1 in the presence of FSH, IL-1 significantly augmented the forskolin-induced secretion of progesterone and accumulation of cAMP after 72 h at subsaturating doses of forskolin. Thus, IL-1 appeared to inhibit forskolin-induced and cholera toxin-induced formation of LH receptors even when cAMP levels were elevated. Similar to forskolin, 8-bromo cAMP-stimulated progesterone secretion was significantly enhanced by IL-1, but LH receptor formation was inhibited. Over a 72-h time course at single doses of FSH or forskolin, IL-1 did not affect cAMP accumulation until 48 h of culture, at which time IL-1 significantly suppressed FSH-induced, but augmented forskolin-induced, accumulation of cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Discordance in the effects of interleukin-1 on rat granulosa cell differentiation induced by follicle-stimulating hormone or activators of adenylate cyclase. 314 56

Normal corpus luteum function is determined by function in the follicular as well as the luteal phase. In the follicular phase adequate follicle-stimulating hormone (FSH) and oestrogen stimulation are required for granulosa cell mitosis and luteinizing hormone (LH) receptor synthesis. An increase in LH pulse frequency may also be necessary for adequate oestrogen synthesis and preparation of follicular cells for luteinization and secretion of progesterone. The nature of LH release may also influence luteal function and pre-ovulatory progesterone may increase the responsiveness of the follicle to gonadotrophins. The thecal vascular network becomes extensive around pre-ovulatory follicles and may influence access of gonadotrophins and/or the ability of follicular cells to respond to them. Further vascularization is an early feature of luteinization. Angiogenic factors are found in luteal tissue and prostacyclin increases luteal blood flow. The corpus luteum consists of large cells which secrete most of the progesterone and have prostaglandin F2 alpha receptors and small cells which are responsive to LH. In the luteal phase subnormal luteal function has not been associated with a reduction in LH concentration, pulse frequency or amplitude. The number and occupancy of LH receptors and adenylate cyclase activity do not appear to be altered by a reduction in luteal function. Low density lipoprotein provides the substrate and somatomedin C modulates among other hormones' influences, progesterone production. In addition to the cAMP second messenger system phosphatidyl inositol metabolism may also be associated with LH stimulation. Luteolysis is an active process; prostaglandin F2 alpha or lipoxygenase products and possibly an endogenous GnRH-like ovarian hormone may mediate it as also may oxytocin in some species.
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PMID:The corpus luteum. 328 62

The effect of germ cells or germ cell fractions on adenylate cyclase (AC) activity in membrane preparations from cultured rat Sertoli cells has been examined. Whole germ cells or 30,000 X g pellet or supernatant fractions of germ cells have the ability to stimulate Sertoli cell AC to levels comparable to those measured in follicle-stimulating hormone-stimulated Sertoli cell membranes. Treatment at 100 degrees C but not 60 degrees C for 1 min abolished the ability of germ cell preparations to stimulate Sertoli AC. Germ cell stimulation of Sertoli cell AC was not calcium dependent, was not blocked by propranolol, and was observed to be dose dependent.
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PMID:Stimulation of rat Sertoli cell adenylate cyclase by germ cells in vitro. 393 81

A near-maximal dose (20 ng/ml) of synthetic luteinizing hormone(LH)-releasing hormone/follicle-stimulating hormone(FSH)-releasing hormone added to incubated anterior pituitary tissue of male rats leads to concomitant increases of intracellular concentrations of adenosine 3':5'-monophosphate and of release of both LH and FSH. The stimulatory effect of LH-releasing hormone/FSH-releasing hormone is observed after a lag period of about 90 min and is progressive at later time intervals; a 3-fold stimulation of cAMP accumulation over control is seen after 210 min of incubation. Half-maximal stimulation of cAMP accumulation is observed between 0.1 and 1.0 ng/ml (0.1-1 nM) of LH-releasing hormone/FSH-releasing hormone. In the presence of 10 mM theophylline, the stimulatory effect of LH-releasing hormone/FSH-releasing hormone on cAMP accumulation is similar to that observed in the absence of the inhibitor of cyclic nucleotide phosphodiesterase, indicating that the releasing hormone exerts its effect by specific activation of adenylate cyclase in LH- and FSH-secreting cells rather than by inhibition of cyclic nucleotide phosphodiesterase. Since the release of growth hormone, thyrotropin, prolactin, and adrenocorticotropic hormone is not affected by LH-releasing hormone/FSH-releasing hormone, and since cAMP stimulates the release of all six adenohypophyseal hormones. the observed changes of cAMP concentrations indicate specific stimulation of adenylate cyclase activity in LH-and FSH-secreting cells of the adenohypophysis.
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PMID:Stimulation of adenosine 3':5'-cyclic monophosphate accumulation in anterior pituitary gland in vitro by synthetic luteinizing hormone-releasing hormone. 434 5


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