Adenylate cyclase in the corpus luteum of the rhesus monkey. iii. changes in basal and gonadotropin-sensitive activities during the luteal phase of the menstrual cycle

The activity of adenylate cyclase was examined in corpora lutea (CL) obtained from rhesus monkeys at specific stages in the luteal phase of the menstrual cycle [3–5, 6–8, 9–12, 13–15, and 16 days (menses) after the midcycle LH surge]. The conversion of [a-³²P]ATP to [³²P]cAMP was used to monitor adenylate cyclase activity. cAMP production in luteal homogenates was assessed in the absence (basal activity) and presence of maximum stimulatory doses of forskolin (100 μM), 5’-guanylylimidodiphosphate [GMP-P(NH)P; 50 μM], GTP (50 μM), and GTP plus increasing doses of hLH and hCG. Basal activity was low in the early luteal phase (days 3–5; mean ± SE, 1.2 ± 0.2 pmol cAMP/mg protein min), increased (P < 0.05) by the midluteal phase (days 6–8 and 9–12, 2.1 ± 0.4 and 2.0 ± 0.3 pmol/mg-min, respectively), and then declined (P < 0.05) during the late luteal phase (days 13–15 and 16-menses, 1.6 ± 0.3 and 1.2 ± 0.5 pmol/mg-min, respectively). Activity stimulated by GTP and GMP-P(NH)P [e.g. GMP-P(NH)P ∼12 times basal level] followed the same pattern as basal activity during the luteal phase. In contrast, cAMP production in the presence of forskolin did not change significantly throughout the luteal phase. In the midluteal phase (days 6–8 and 9–12; n = 12), hCG and human LH (hLH) stimulated adenylate cyclase in a similar dose-dependent manner. Maximal stimulation of cAMP production by hCG was about 10% greater (P < 0.05) than that by hLH; the activation constant was 12.3 nM for hCG and 28.3 nM for hLH. The maximal response to hLH and hCG as well as the sensitivity of adenylate cyclase to activation by hLH were greater (P < 0.05) in the midluteal phase than in the early or late luteal phase. Decreased basal, gonadotropin-stimulated, and guanine nucleotide-stimulated cAMP production and diminished sensitivity of adenylate cyclase to hLH correlated with a decline (P < 0.05) in circulating progesterone and luteal weight during the late luteal phase. Thus, the adenylate cyclase system of the rhesus monkey CL undergoes significant changes during the luteal phase which are associated with the development and regression of the CL of the menstrual cycle. Mechanisms that modulate gonadotropin and nucleotide activation of adenylate cyclase without interfering directly with the catalytic unit are implicated in the changes that accompany luteolysis.