Endocrinology: Stimulation of ovarian adenylyl cyclase activity by gonadotrophins during the natural and gonadotrophin-induced cycles in the hamster

In this study we utilized the hamster ovary as a model to investigatethe effects of ovulation induction with gonadotrophin on theactivation of the signal transducer effector system, adenylylcyclase (AC). For this purpose, we prepared membrane particlesfrom the ovary and analysed both gonadotrophin-sensitive ACand non-receptor-mediated activation during a cycle in whichovulation and luteinization were achieved by pregnant mare’sserum gonadotrophin (PMSG)/human chorionic gonadotrophin (HCG)administration. Results were directly compared with AC activationin similarly prepared membranes obtained at different stagesof the natural unstimulated cycle. AC activity was quantifiedby the direct conversion of ATP substrate into cyclic adenosinemonophosphate (cAMP). Measurements of ovarian weights, serumoestradiol and progesterone concentrations provided a solidbase from which to evaluate the functional status of the ovaryat each time period during the natural and stimulated cycles.We found that ovarian membranes contain functional componentsof the AC system and demonstrated that AC is highly dependenton hormonal changes and the functional state of the ovary. Thus,during the natural cycle, ovarian AC showed relatively constantresponsiveness to follicle-stimulating hormone (FSH) throughoutthe cycle, whereas responsiveness to luteinizing hormone (LH)/HCGreached its peak during the luteal phase. On the other hand,during the stimulated cycle, sensitivity to FSH and LH/HCG variedconsiderably, being absent during the peri-ovulatory period.AC responsiveness to gonadotrophins was only regained 48 h afterovulation. Also during the peri-ovulatory period of the gonadotrophin-inducedcycle, stimulation of ovarian AC with non-hormonal activatorsdeclined. However, the rate of cAMP production in response tothese activators remained very high, indicating that despiterefractoriness to gonadotrophins, ovarian AC retained the capacityto generate cAMP at near maximal efficiency. Basal (non-stimulated)activity, guanine nucleotide activation, hormone responsivenessand stimulation by the non-hormonal activators NaF and forskolinwere all significantly increased in comparison with the naturalcycle. Basal activity alone was 7-fold higher than the activityobserved during the unstimulated cycle. These results suggestthat subsequent to exogenous gonadotrophin administration, thetransmembrane effector AC system must be primed for a higherlevel of activity in the ovarian tissue. This priming of theovarian AC system by exogenous gonadotrophin was also evidentwhen the enzyme was measured under conditions allowing maximalactivity, i.e. in the presence of a combination of NaF and forskolin.Maximal AC activity increased 4- to 5-fold compared with thenatural cycle. We conclude that gonadotrophin administrationinducing ovulation causes profound alterations in the expressionof AC in ovarian membranes. Gonadotrophin treatment increasedthe enzyme activity and induced a temporal desensitization toFSH and LH/HCG in the peri-ovulatory period of the stimulatedcycle. Because the gonadotrophin-sensitive AC system representsthe capacity of FSH and LH/HCG receptors to couple and elicita biological response, our results provide new insights intothe cellular mechanisms that regulate ovarian activity duringinduction of ovulation.