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

---

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

The regulation by cAMP of cholesterol side-chain cleavage activity and the synthesis of immunoisolated cytochrome P-450scc and adrenodoxin proteins was investigated in primary cultures of swine ovarian (granulosa) cells. Administration of a novel adenylate cyclase toxin isolated from Bordetella pertussis increased granulosa-cell cAMP accumulation up to 200-fold over basal. These effects were additive with those of FSH, forskolin, and cholera toxin. In contrast, bacterial extracts BP 347 and BP 348 from mutant strains of B. pertussis that lack either all virulent factors or the adenylate cyclase toxin and hemolysin were devoid of effect. Granulosa-cell cAMP accumulation supported by active bacterial adenylate cyclase was accompanied by 2- to 11-fold, time-dependent increases in [35S]methionine incorporation into immunospecific cytochrome P-450scc and adrenodoxin. These increases in the synthesis of cholesterol side-chain cleavage proteins were associated with enhanced pregnenolone production in response to exogenous sterol substrate, 25-hydroxycholesterol, and augmented progesterone secretion both in the absence and presence of exogenous lipoprotein. Moreover, the effects of Bordetella adenylate cyclase toxin on granulosa cell steroidogenesis were functionally integrated with other regulatory responses, since the non-cAMP dependent effector, estradiol 17-beta, interacted synergistically with bacterial adenylate cyclase in stimulating progesterone production. We conclude that exogenous adenylate cyclase isolated from B. pertussis can be functionally integrated into the cAMP-dependent effector pathway of granulosa cells with a resulting increase in intracellular cAMP concentrations, augmented biosynthesis of progesterone and pregnenolone, enhanced synthesis of immunospecific cytochrome P-450scc and adrenodoxin, and synergistic interactions with a non-cAMP-dependent ovarian effector hormone (estradiol).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Actions of cyclic adenosine monophosphate on the cytodifferentiation of ovarian cells: studies in cultured swine granulosa cells using a novel exogenous adenylate cyclase from Bordetella pertussis. 284 59

Mixed cell preparations (theca plus granulosa) prepared from the hierarchy of follicles of quails ovaries were incubated under defined conditions with or without the addition of ovine luteinizing hormone (oLH), ovine follicle stimulating hormone (oFSH), theophylline, cycloheximide, or dibutyryl cyclic adenine monophosphate (db cAMP); or in the presence of androstenedione or testosterone as aromatizable substrate. Steroids secreted into the medium during the 4-hr incubation period were assayed by radioimmunoassay. Cells from the largest follicles (F1) secreted predominantly progesterone, were stimulated by LH and db cAMP, and the response was potentiated by theophylline, but FSH had no stimulatory effect. The F1 cells showed increasing basal and LH-stimulated responses between 18 and 12 hr before the next expected oviposition. Cells from the smaller follicles (F3 and F4) secreted predominantly estrogens, and were stimulated by FSH but not by db cAMP and only to a small extent by theophylline. Addition of androstenedione (10(-7) M) or testosterone (10(-7) M) enhanced estrogen secretion, which was further raised by the simultaneous addition of FSH. These results confirm previous reports on the sites of steroid secretion within quail follicles and suggest that while the action of LH on the cells from F1 follicles may be mediated in part through the adenylate cyclase system, the action of FSH on the smaller follicles may be substantially independent of cAMP.
...
PMID:Steroid secretion by ovarian cells of the Japanese quail (Coturnix coturnix japonica). 284 45

Although estradiol (E2) alone does not increase receptors for FSH in granulosa cells, E2 priming before administration of FSH increases numbers of FSH receptors significantly compared with FSH alone. We hypothesized that if E2 is required for FSH to increase its own receptor, blocking estrogen action should prevent FSH-induced increases in FSH receptors. Five groups of hypophysectomized rats were injected sc with: saline at 0 h; the antiestrogen CI628 (1 mg) at -6 h; human FSH (hFSH, 2 micrograms) at 0 h; CI628 at -6 h, then hFSH at 0 h; and CI628 plus E2 (2 mg) at -6 h, then FSH at 0 h. Animals were decapitated at 0, 6, 12, or 24 h, and granulosa membrane receptors for FSH, LH, and nuclear receptors for E2 were measured. LH receptor levels increased only after administration of E2 before hFSH. Treatment with hFSH for 6 h increased numbers of FSH receptors 3-fold (P less than 0.01) without any increase in numbers of E2 receptors. At 12 and 24 h, hFSH increased numbers of FSH and E2 receptors 6- and 7-fold (P less than 0.01) over controls. CI628 prevented the hFSH-induced increases in FSH receptors at 6, 12, and 24 h. Administration of E2 concomitant with CI628 before hFSH significantly reversed the inhibitory effects of CI628 on hFSH-induced increases in FSH receptors. There were no changes in affinity of FSH or E2 receptors from 0 to 24 h. To determine whether E2 was acting on the adenylate cyclase system, the ability of hFSH to increase the content of cAMP in granulosa cells in each treatment group was determined. After an iv injection of hFSH, cAMP levels were similar in CI628- and saline-treated rats but had increased 6-fold (P less than 0.01) in hFSH or CI628 plus hFSH-treated animals. Thus, blocking hFSH-induced increases in FSH and E2 receptor appeared to have no effect on FSH stimulation of cAMP. In conclusion E2 appears to be required for FSH action, perhaps by acting within granulosa cells distal to the cAMP-adenylate cyclase system.
...
PMID:CI628 inhibits follicle-stimulating hormone (FSH)-induced increases in FSH receptors of the rat ovary: requirement of estradiol for FSH action. 298 76

Whether peptide hormones other than ACTH may be responsible for the difference in size or rate and pattern of steroidogenesis of the fetal zone (FZ) compared to those of the neocortex (NC) of the human fetal adrenal gland is controversial. In the present investigation, the activity of adenylate cyclase in membrane fractions of separated zones of the human fetal adrenal gland was determined. Basal adenylate cyclase activity was 2- to 3-fold greater in NC than in FZ membrane fractions. The addition of ACTH-(1-24) stimulated adenylate cyclase activity in both zones, but the activity was more sensitive to ACTH (10(-10) M) in NC fractions than in FZ fractions (10(-7) M). In addition to ACTH-(1-24), the effect of other ACTH-related peptides on the activity of adenylate cyclase in the separated zones of the adrenal gland was investigated. 16K fragments 2-36, gamma 3MSH, alpha MSH, beta-endorphin, leu-enkephalin, and met-enkephalin, as well as hCG, FSH, prostaglandin E2, prostaglandin F2 alpha, epinephrine, and norepinephrine did not stimulate adenylate cyclase activity in either zone. It is concluded that basal and ACTH-(1-24)-stimulated adenylate cyclase activities are greater in NC than in FZ membrane fractions. In addition, the results of the present investigation do not support the concept that other ACTH-related peptides or peptide or protein hormones increase steroidogenesis by stimulating adenylate cyclase activity in the human fetal adrenal gland.
...
PMID:Adenylate cyclase activity in neocortex and fetal zone membrane fractions of the human fetal adrenal gland. 298 5

Addition of glucagon to the incubation medium of cultured Sertoli cells isolated from immature (19-day-old) rats resulted in a time- and concentration-dependent stimulation of cAMP accumulation measured both in the cells and in the medium. Maximal intracellular levels of cAMP were reached after 30 min, after which the levels decreased. In the medium cAMP levels reached a plateau after 6 h. The magnitude and kinetics of the responses were comparable to those observed with FSH in the same culture preparations. 1-Methyl-3-isobutylxanthine (MIX), a phosphodiesterase inhibitor, greatly potentiated the magnitude of the effects of glucagon and FSH. Glucagon stimulated adenylate cyclase activity in isolated membrane preparations from similar cultures, and the concentration causing half-maximal stimulation (EC50) was approximately 300 ng/ml. Glucagon also stimulated aromatization in cultured Sertoli cells to the same extent as FSH. It is concluded that cultured Sertoli cells isolated from immature rats contain receptors for glucagon, coupled to adenylate cyclase, and that glucagon also stimulates aromatization of testosterone to estradiol.
...
PMID:Glucagon-stimulated cyclic AMP production and formation of estradiol in Sertoli cell cultures from immature rats. 298 57

In the present study, we have examined the effects of two adenosine analogs, (-)N6-(R)phenyl-isopropyl-adenosine (PIA) and 2-chloro-adenosine, on glucagon- and FSH-stimulated cAMP production in Sertoli cell cultures isolated from immature (19-day-old) rats. Both FSH and glucagon caused a 5- to 10-fold stimulation of cAMP levels in the spent media from Sertoli cell cultures during an 18-h incubation. Addition of 1 microM PIA significantly inhibited both FSH- and glucagon-stimulated cAMP levels. In the presence of a maximal concentration of glucagon (2.5 micrograms/ml), PIA caused a concentration-dependent inhibition of cAMP formation, and the concentration of PIA causing half-maximal inhibition of cAMP formation (IC50) ranged from 0.5-1 nM. When Sertoli cells were incubated with increasing concentrations of glucagon (1.28 ng/ml to 4.00 micrograms/ml) in the absence and presence of either PIA (1.0 microM) or 2-chloro-adenosine (10.0 microM), the responses to glucagon, measured as cAMP formation, were almost completely abolished. 1-Methyl-3-isobutylxanthine (MIX), a well known inhibitor of cAMP phosphodiesterase activity, is also an inhibitor of adenosine binding to receptors on the cell membrane. When Sertoli cells stimulated with glucagon (2.5 micrograms/ml) were incubated in the absence and presence of MIX (0.1 mM) and increasing concentrations of PIA (0.025-10,000 nM), the presence of MIX reduced the inhibitory activity of PIA by almost 2 orders of magnitude (IC50 without MIX, 0.5 nM; IC50 with MIX, 20 nM). Thus, the present study shows that adenosine analogs inhibit agonist-stimulated cAMP formation in cultured Sertoli cells, and that MIX reduces this effect. This indicates that cultured Sertoli cells from immature rats contain A1-receptors for adenosine mediating inhibitory effects on adenylate cyclase.
...
PMID:Effects of adenosine analogs on glucagon-stimulated adenosine 3',5'-monophosphate formation in Sertoli cell cultures from immature rats. 299 Aug 52

Ovarian granulosa cells from small follicles have generally been considered to comprise a homogeneous cell population; however, stratified arrangements of hormone receptors have been found in antral and mural granulosa cells of Graafian follicles. Using cultured granulosa cells derived from immature, hypophysectomized, estrogen-treated rats, we have previously shown that vasoactive intestinal peptide (VIP) as well as FSH stimulates steroid production by these cells. Dose-response analysis indicated that the actions of these hormones were additive, suggesting the presence of subpopulations of granulosa cells. Using a continuous (0-30%) Metrizamide density gradient, we have identified three populations of granulosa cells with different sedimentation properties. After centrifugation for 15 min at 1500 X g, cells sedimented at Metrizamide concentrations of 13%, 18%, and 20% (peaks A, B, and C, respectively). The subpopulation with lowest density (peak A) comprised 5% of the total cells, whereas the remaining cells were distributed approximately equally in the other two peaks. The profiles of estrogen and progesterone production by these cells in response to FSH and VIP indicated that FSH preferentially stimulated steroid production in cells with the highest density (peak C), whereas VIP mainly induced steroidogenic responses in cells of intermediate density (peak B). In contrast, cells with the lowest density (peak A) were unresponsive to either hormone. Treatment with forskolin, a universal adenylate cyclase activator, induced steroid production in both subpopulations B and C. Further studies demonstrated that LH/human CG receptors were induced by FSH and forskolin in cells from peak C, whereas VIP treatment did not induce LH/human CG receptors in cells from peak B. In unfractionated cultured cells, GnRH potently antagonized FSH- but not VIP-induced steroidogenesis. Upon density-gradient fractionation, the profile of GnRH receptor content correlated well with GnRH effects since FSH-responsive cells (peak C) contained the majority of GnRH receptors. The present results demonstrate that granulosa cells from immature follicles are heterogeneous and consist of two major subpopulations of cells with differential responsiveness to FSH and VIP. These findings provide the basis for further morphological and biochemical analysis of subpopulations of granulosa cells during follicular development.
...
PMID:Identification of subpopulations of rat granulosa cells: sedimentation properties and hormonal responsiveness. 299 Aug 65

The actions of dioctanoylglycerol, a novel and specific activator of protein kinase C, on granulosa cell steroidogenesis and LH/hCG receptor induction were examined in vitro. Granulosa cells were cultured for 2 days in media containing 100 nM androstenedione. FSH treatment stimulated progesterone, 20 alpha-hydroxy-pregn-4-en-3-one (20 alpha-OH-P) and estrogen production by 60- to 80-fold over basal levels. Treatment with dioctanoylglycerol increased progesterone production 3-fold over basal levels but failed to affect 20 alpha-OH-P or estrogen production. Concomitant treatment of cells with FSH and increasing amounts of dioctanoylglycerol produced dose-dependent inhibition of FSH-stimulated progesterone, 20 alpha-OH-P and estrogen production with IC50 values of 75, 40 and 50 microM, respectively. Dioctanoylglycerol also inhibited production of all three steroids induced by forskolin, an activator of adenylate cyclase, and dibutyryl cAMP. The effects of dioctanoylglycerol on cAMP responses to FSH were also examined. The increase in both intracellular and extracellular cAMP at 1 h following treatment with FSH was suppressed in the presence of dioctanoylglycerol as was the extracellular accumulation of cAMP at 48 h of culture. FSH induction of LH/hCG receptors, known to be a cAMP-mediated event, was also inhibited in the presence of dioctanoylglycerol. In contrast, a thio-derivative of dioctanoylglycerol (3-thio-1,2-dioctanoylglycerol), which does not activate protein kinase C, failed to inhibit both steroidogenesis and LH/hCG receptor induction in response to FSH.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Inhibition of granulosa cell differentiation by dioctanoylglycerol--a novel activator of protein kinase C. 299 79

Basal and gonadotropin stimulated adenylate cyclase activity was assessed in testicular tissues obtained from men (20-80 years). A disparity was observed in the gonadotropin responsiveness of the human testicular adenylate cyclase system to hFSH and hCG stimulation. Of the tissues analyzed, 61% were FSH responsive and 22% showed low response to hCG. Forskolin, a diterpene which activates adenylate cyclase by a receptor independent mechanism, stimulated adenylate cyclase activity in the gonadotropin unresponsive tissues. This suggests that the tissue unresponsiveness is due to an uncoupling of the catalytic subunit of the adenylate cyclase. Several functional properties of the FSH responsive human testicular adenylate cyclase were investigated. hFSH and oFSH stimulated the enzyme activity in a concentration dependent manner. However, the hormone (DG-oFSH) in which 80% of the carbohydrate residues had been removed was inactive, despite its good binding ability to the FSH receptor. hFSH stimulated adenylate cyclase activity was inhibited by DG-oFSH but not by DG-hCG (deglycosylated hCG). The data demonstrates the existence of specific FSH and LH(hCG) receptors in human testicular membranes. The FSH receptors in some tissues are coupled to adenylate cyclase. The link between the FSH receptor and adenylate cyclase may be uncoupled in the presence of the deglycosylated form of oFSH resulting in a loss of hormone response.
...
PMID:Characterization of gonadotropin-sensitive adenylate cyclase activity in human testis: uncoupling of the receptor-cyclase complex by specific hormonal antagonist. 299 80

The objective of this study was to characterize the corpora lutea (CL) of superovulatory follicles, which form in nonhuman primates after treatment with exogenous gonadotropins. Adult female rhesus monkeys (n = 15) with amenorrhea or irregular menstrual cycles received im injections of either human menopausal gonadotropin [hMG; equivalent amounts (37.5 IU) of hFSH and hLH] or human FSH (37.5 IU) twice daily for 6 or 9 days. One day later, hCG (1000 IU) was administered to induce ovulation. Serum estradiol levels rose rapidly in hMG-treated monkeys. In contrast, estradiol levels did not rise in FSH-treated animals for 3-4 days, but ultimately reached concentrations comparable to or greater than those in hMG-treated monkeys. Serum progesterone levels were low in all groups before hCG injection, but rose thereafter. Peak progesterone levels were greater (P less than 0.05) in 9- vs. 6-day treatment groups. Serum concentrations of hCG peaked within 24 h of injection and declined to undetectable levels 6-7 days later. The mass of luteinized tissue removed 7 days after hCG injection was markedly (P less than 0.01) increased in hMG- and FSH-treated monkeys compared to that of the active CL of the natural menstrual cycle (n = 6). However, the protein content of luteal tissue from FSH-treated monkeys was less (P less than 0.05) than that in hMG-treated groups or in the CL of the natural cycle. Luteal particulate fractions from all treatment groups had [125I]human LH binding sites, with the Kd for LH interaction comparable to that in the CL of the natural cycle. However, the LH-binding capacity in hMG-treated groups was less (P less than 0.05) than that in the CL of the cycle, when normalized per mg tissue wt or protein. Notably, the binding capacity in FSH-treated groups was comparable to that in the CL cycle when expressed per mg protein. Nevertheless, only after 6 days (not 9 days) of FSH treatment or 9 days (not 6 days) of hMG treatment did tissues have a LH-sensitive (activation constant) or LH-responsive adenylate cyclase comparable to that in the CL of the cycle. Thus, properties of the primate CL after superovulation varied markedly with the type and length of gonadotropin treatment employed for follicular stimulation. The findings support the concept that gonadotropin-regulated events in the developing follicle(s) are important determinants of the subsequent character of the primate CL.
...
PMID:Characterization of corpora lutea in monkeys after superovulation with human menopausal gonadotropin or follicle-stimulating hormone. 300 56


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

---