Maturation of adrenocorticotropin-sensitive adenylate cyclase of ovine fetal adrenal during late pregnancy.
The number of ACTH-(1-24) receptors and the adenylate cyclase (AC) responsiveness to several stimuli have been measured in crude adrenal membranes from fetal and newborn lambs. At 124 days of gestation, the number of ACTH-(1-24)-binding sites was 51 +/- 9 (SE) pmol/microgram DNA, and AC was stimulated by 2 x 10(-2) M NaF (195 +/- 5%) and 10(-5) M guanosine (beta, gamma-imido) triphosphate [Gpp(NH)p]; (168 +/- 8%) but not by 10(-6) M ACTH-(1-24). However, when Gpp(NH)p was added to ACTH-(1-24), the response was significantly higher than with Gpp(NH)p alone. On the contrary, at 140 days, despite no increase in the number of ACTH-(1-24) receptors, AC was stimulated by ACTH-(1-24) (135 +/- 6%), and Gpp(NH)p enhanced this response. In addition, the response to NaF and to Gpp(NH)p alone was higher at 140 than at 124 days. Between day 140 of gestation and birth, the stimulation of AC by ACTH-(1-24) and ACTH-(1-24) plus Gpp(NH)p increased, but the response to NaF and to Gpp(NH)p alone did not. During the same time, the number of ACTH-(1-24) receptors was increased by a factor of 3. No change in the Kd and Km of ACTH-(1-24) was observed during the period studied. Neither prostaglandin E2 (10(-5) M) nor alpha MSH (10(-6) M) stimulated AC at any stage. The relative insensitivity of AC before 140 days can thus be related to 1) a defect of availability of GTP, and 2) a low activity of the catalytic subunit of AC (subunit C) or, alternatively, a defect in the GTP-binding component (subunit N). The increased sensitivity to ACTH-(1-24) of the enzyme just before parturition correlates closely with an increase in the number of ACTH-(1-24) receptors.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000311:Adrenal Glands / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D003366:Cosyntropin / Q000494:pharmacology; D005260:Female; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D011247:Pregnancy; D011458:Prostaglandins E / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D018043:Receptors, Corticotropin; D012756:Sheep; D012969:Sodium Fluoride / Q000494:pharmacology
D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D018043:Receptors, Corticotropin; D003366:Cosyntropin; D006165:Guanylyl Imidodiphosphate; D012969:Sodium Fluoride; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones; D000262:Adenylyl Cyclases