Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the last month of intra-uterine life, the steroidogenic response of the ovine fetal adrenal glands to ACTH increases and becomes maximal at the time of birth. This development involves modifications at different steps of the adrenocorticotropic hormone (ACTH) action mechanism. It has been shown that the enhanced capacity of the cells to produce cAMP is related to at least three factors: an increased number of ACTH receptors, increased activity of the Ns subunit of adenylate cyclase, and enhancement of guanosine 5'-triphosphate (GTP) availability. The ability to produce pregnenolone and the activity of both 3 beta-hydroxy steroid dehydrogenase/isomerase and 17 alpha-hydroxylase are mainly enhanced in the steroidogenic pathway. The infusion of ACTH for 5 days into 115 to 120-day old fetuses results in the development of most of these biochemical process. Similarly, ACTH can induce maturation of cultured fetal adrenal cells and some other proopiomelamocortin (POMC)-derived peptides can potentiate its acute steroidogenic activity in vitro. However, even in the absence of ACTH, the adenylate cyclase system and the steroidogenic potency of cultured cells increase but to a lesser extent than when ACTH is present in the culture medium. It is suggested that ACTH is the main trophic hormone of the ovine fetal adrenal during the last month of gestation, even if other stimulatory factors may also be important. The in vivo maturation of ovine fetal adrenal is blocked by the presence of some unknown inhibitory factors in the fetal circulation which are of likely extrapituitary origin.
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PMID:Biochemical modifications involved in the maturation of the ovine fetal adrenal gland in late gestation: their modalities and regulation. 300 80

Mycotoxins as contaminants of animal food can impair fertility and can cause abnormal fetal development in farm animals. Therefore, the present study has investigated whether derivatives of the mycotoxin zearalenone, alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL), influence progesterone synthesis via cytochrome p450 side chain cleavage enzyme (p450scc) and 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) in cultured porcine granulosa cells. Both enzymes are essential for the conversion of cholesterol to progesterone. No differences in basal progesterone levels and numbers of viable cell were observed between untreated granulosa cells and those treated with alpha- or beta-ZOL (15 and 30 microM). FSH (0.01 microg/ml) or forskolin (10 microM) enhanced the basal progesterone secretion in the absence of mycotoxins. The addition of alpha- or beta-ZOL (7.5, 15 and 30 microM) to cultures stimulated with FSH (0.01 microg) or forskolin (10 microM) reduced progesterone synthesis and the levels of p450scc and 3beta-HSD transcripts in a dose-dependent manner (P<0.05). The enzymatic activity of 3beta-HSD and the abundance of p450scc protein were also reduced by these mycotoxins. In conclusion, effects of mycotoxins on FSH receptor-dependent and receptor-independent pathways indicate that adenylate cyclase activity and/or regulatory pathways further downstream are targets of mycotoxin actions. The apparent dose-dependent reduction of p450scc and 3beta-HSD transcripts implies an effect of alpha- and beta-ZOL on transcriptional regulation of these enzymes.
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PMID:Effects of the mycotoxins alpha- and beta-zearalenol on regulation of progesterone synthesis in cultured granulosa cells from porcine ovaries. 1461 19

Cytokines might regulate the function of the hypothalamic-pituitary-adrenal axis. IL-15 is a potent non-T-cell-derived cytokine with IL-2-like activities. It has been shown that IL-15 can reverse the inhibition of glucocorticoids on PBMC. In vitro experiments were designed to assess the direct effect of IL-15 on corticosterone (CORT) secretion in the adrenal zona fasciculata-reticularis (ZFR) cells of male rats. Administration of IL-15 dose dependently decreased the basal and adrenocorticotropin-stimulated release of CORT and production of cAMP in ZFR cells. The stimulatory effect of forskolin (an adenylate cyclase activator) on CORT secretion and accumulation of cAMP in ZFR cells was attenuated by the administration of IL-15. However, 8-Br-cAMP (a cAMP analogue)-stimulated release of CORT was not affected by IL-15. Exogenous administration of IL-15 (10(-7) mol/L) significantly attenuated the pregnenolone (the substrate of 3beta-hydroxysteroid dehydrogenase)- or deoxycorticosterone (the substrate of 11beta-hydroxylase)-induced release of CORT. The results indicate that decrease of CORT secretion by IL-15 is in part because of (i) the decrease of adenylate cyclase activity and cAMP production and (ii) the inhibition of 3beta-hydroxysteroid dehydrogenase and 11beta-hydroxylase activities in rat ZFR cells.
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PMID:Direct effects of IL-15 on corticosterone secretion by rat adrenocortical cells. 1640 51

Age-related decline in male sex hormones is a direct consequence of testicular aging. These changes in the hormonal complement cause physiological disturbances affecting the quality of life for millions of aging men. To assess the influence on testicular aging of pituitary adenylate cyclase-activating peptide (PACAP), a polypeptide that regulates testicular steroidogenesis in vitro, we compared the testicular structure and function between C57BL/6 wild-type and PACAP-/- male mice, at 4 and 15 months of age. We show that, in 4-month-old PACAP-/- mice, steroidogenesis (evaluated by levels of testosterone, steroidogenic acute regulatory protein, 3beta-hydroxysteroid dehydrogenase, and P450c17) was impaired. However, the testicular structure of these animals was not affected. At 15 months of age, wild-type testis displayed typical signs of aging (patchy seminiferous tubules, germ cell depletion, and vacuolization), whereas testicular structure was remarkably well conserved in PACAP-/- animals. The depletion of germ cells found in wild-type animals was associated with a higher content of peroxynitrites, a marker of reactive oxygen species, and a higher number of apoptotic cells compared with PACAP-/- mice. Our results show that testicular aging is delayed in PACAP-/- animals. Because the expression levels of steroidogenic factors are low and constant over time in knockout animals, a proposed mechanism for the protection against testicular degeneration is that production of reactive oxygen species, a byproduct of steroidogenesis that induces apoptosis, is down-regulated in PACAP-/- animals.
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PMID:Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice. 1650 86