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)

Here, we chronologically analyzed age-associated changes of cAMP- and MAPK-signaling in Leydig cells (LCs) in relation with decreased testosterone (T) production. In Wistar rats, decreased serum T observed in 12 to 24-month-old rats was not related to decreased serum LH concentration but to reduced luteinizing hormone receptor (Lhr/LHR) and time-coordinated reduction of steroidogenic gene expression (decreased Cyp11a1, Cyp17a1 in 12-month-old rats followed by decreased Star/StAR, Hsd3b/HSD3B, Hsd17b4, and increased Cyp19a1 later in life). The predecessors of age-related changes noted in LCs from 6 to 12-month-old rats were increased level of soluble adenylate cyclase (Adcy/AC) 10, increased JNK phosphorylation but suppressed P38 MAPK. At approximately the same time changed mRNA abundance for transcription factors important for steroidogenesis was detected (increased Nur77 and decreased Sf1, Dax1). Aging caused biphasic expression pattern of ERK1/2 and Nur77: increased in 12-month but decreased in LCs from 24-month-old rats. Further, decreased basal cAMP level observed from 12 to 24th month coincidence with increased expression of cAMP-specific phosphodiesterase (Pde)4a, Pde4b and regulatory subunit of protein kinase A (Prkar/PKAR). Exposing of senescent LCs to permeable cAMP-analog improved transcription of Sf1, Nur77, Star, Cyp11a1,Cyp17a1, but without effect on aging pattern of Dax1, Pde4a/b, Prkar2a, Lhr and MAPK genes. Collectively, results indicated that age-related LC dysfunction is accompanied with changes in MAPK and cAMP signaling and coordinated reduction in the expression of many of the genes that participate in T synthesis. The predecessors of aged-related changes are increased ratio of pJNK/JNK, AC10 and decreased P38 level in LCs from 6-month-old rats.
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PMID:Age related changes of cAMP and MAPK signaling in Leydig cells of Wistar rats. 2501 73

Transcription factors, runt-related transcription factor 1 (RUNX1) and 2 (RUNX2), belong to the runt-related (RUNX) gene family and play critical roles in mammalian reproduction processes. However, the regulatory mechanisms of RUNX1 and RUNX2 expression or their functions in goat follicles remain largely unknown. Herein, RUNX1 and RUNX2 proteins were detected in the oocytes and granulosa cells of preantral and antral follicles, as well as corpus luteum by immunohistochemistry. Treatments with human chorionic gonadotropin (hCG) or with the agonists and inhibitors of hCG-induced intracellular signaling pathways in granulosa cells in vitro, we found that hCG increased RUNX1 expression by activating PKC and PI3K signaling molecules, and increased RUNX2 expression by activating adenylate cyclase, PKC, and PI3K signaling molecules. We also demonstrated that miR-181b expression is dependent on the hCG-induced activation of PKC and PKA, and miR-222 expression is dependent on the hCG-induced activation of PI3K and PKC in cultured granulosa cells. Meanwhile, miR-181b and miR-222 suppressed RUNX1 and RUNX2 expression by targeting RUNX1 and RUNX2 3' untranslated regions (3'UTRs) with or without hCG, respectively. These results suggested that hCG-mediated miR-181b and miR-222 expression are important for the regulation of RUNX1 and RUNX2 expression levels in granulosa cells. To explore the specific functions of RUNX1 and RUNX2, we transfected RUNX1 and RUNX2 small interfering RNAs into primary cultured granulosa cells. Knockdown of RUNX1 and RUNX2 significantly decreased progesterone productions and the mRNA abundance of key steroidogenic enzymes (StAR, CYP11A1 and HSD3B) after hCG treatment. But only miR-222 increased estradiol secretion in goat granulosa cells. In addition, knockdown of RUNX1 and RUNX2 also promoted granulosa cell proliferation. The hormonally regulated expression of RUNX1 and RUNX2 in granulosa cells, their involvement in progesterone production, and promoted granulosa cell proliferation suggest important roles of RUNX1 and RUNX2 in follicular development and luteinization.
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PMID:Regulation and function of runt-related transcription factors (RUNX1 and RUNX2) in goat granulosa cells. 2962 8