Testosterone Stimulation of Progesterone Synthesis by Gonadotropin-Desensitized Corpora Lutea*

To determine whether the availability of LH receptors and of an LH responsive adenylyl cyclase (AC) was of importance to corpus luteum (CL) function after midpregnancy, rats were injected daily with 3, 6, 18, or 60 IU of human CG (HCG) between days 12–14. On day 14, only rats treated with 18 or 60 IU ovulated. However, regardless of the dose used, luteal cell content of LH receptor and LH-responsive AC dropped dramatically and epinephrine responsive AC was partially desensitized. Nevertheless, progesterone concentration in the serum remained elevated and pregnancy was maintained in all groups. in vitro determination of luteal cell synthesis of progesterone indicated that despite a desensitized AC, CL of rats treated with nonovulatory doses of hCG produced as much progesterone as CL of rats treated with vehicle. However, after treatment with ovulatory doses of hCG, production of progesterone by the original set of CL was curtailed. To determine whether CL continued to secrete progesterone despite a desensitized AC because of placental secretion of testosterone, rats were hypophysectomized and hysterectomized on day 12 and were treated with two silastic capsules containing testosterone or with the combination of testosterone plus 6 or 60 IU of hCG daily. Fortyeight hours after hypophysectomy and hysterectomy, serum progesterone declined from 126 ± 14 ng/ml to 55 ± 7, LH and epinephrine stimulated AC were suppressed 60 and 80%, respectively, whereas luteal LH receptor remained unchanged. After testosterone treatment, progesterone levels in the serum increased to 118 ± 16 ng/ml and both LH-and epinephrinestimulated AC were maintained at levels found in CL of intact animals. Treatment with 6 IU hCG combined with testosterone induced a 98% drop in LH receptor and a desensitization of AC to both LH and epinephrine. However, progesterone in the serum remained at levels similar to intact pregnant rats (131 ± 24 ng/ml). Rats treated with testosterone and 60 IU hCG also had no luteal LH-stimulated AC; however, progesterone production decreased and serum concentrations were 28 ± 6 ng/ml. In summary, results of this investigation indicate that the availibility of LH and catecholamine-responsive cyclases are not of importance to luteal cell function after midpregnancy and that treatment with ovulatory doses of hCG inhibit the stimulation of progesterone production by testosterone at a step beyond cAMP production.