Gonadotropin-Induced Desensitization of Epinephrine Action in the Luteinized Rat Ovary*

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Abstract
The actions of epinephrine on luteal cell function, and the effects of gonadotropin-induced luteal desensitization upon β-adrenergic responses, were examined in the luteinized rat ovary. Both epinephrine and LH stimulated adenylate cyclase activity in ovarian homogenates and increased the production of cAMP and progesterone in luteal cells. Maximally effective doses of the two hormones did not have an additive effect upon adenylate cyclase activity or steroidogenesis. The actions of epinephrine on adenylate cyclase and progesterone production were inhibited by propranolol but not by phentolamine, and neither adrenergic antagonist influenced the actions of LH. These results indicate that LH and β-adrenergic effectors act through independent receptors on a common pool of adenylate cyclase to stimulate progesterone production in the luteal cell. In ovaries from rats treated with desensitizing doses of hCG, the decreased ability of LH/hCG to stimulate adenylate cyclase activity was accompanied by a transient loss of the enzyme response to epinephrine. In partially desensitized ovaries, there was no change in the half-maximal dose for epinephrine stimulation of adenylate cyclase activity. The loss of enzyme responsiveness to LH/hCG and epinephrine was proportional to the desensitizing dose of hCG. In luteal cells prepared from desensitized tissues, the impaired production of progesterone in response to LH was accompanied by a decreased response to epinephrine. The production of cAMP by isolated luteal cells was correspondingly decreased in response to both ligands. The number of LH receptors was also markedly reduced, but no significant change in the number of β-adrenergic receptors was detected by assay with [3H]dihydroalprenolol. These findings indicate that LH receptor-mediated desensitization of ovarian luteal cells by hCG leads to the loss of responsiveness to both LH and epinephrine. Since the two hormones act via independent receptors to evoke cAMP production and steroidogenesis, these results suggest that desensitization by gonadotropin leads to a defect in the coupling of β- adrenergic receptors to adenylate cyclase.