Gonadotropin-Induced Positive Regulation of Testicular Luteinizing Hormone Receptors

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Abstract
Subcutaneous injections of ovine LH (oLH) caused an acute increase of rat testis LH receptor sites, as measured by in vitro binding of 125I-labeled hCG. There was a concomitant increase in testicular lactogen receptors, and both sets of sites reached a maximum 1 h after hormone injection. The increase was transient, and binding returned to the control level in 1.5–2 h. With increasing doses of oLH, hCG binding increased gradually and was significantly elevated (P < 0.05– 0.01) with doses of 30–1000 μg. The maximum increase in hCG binding averaged 44% when measured in testicular membrane preparations and 93% in collagenase-dispersed Leydig cells. The enhanced binding was due to a true increase in the number of binding sites, with no change in the equilibrium association constant (Ka). The increased binding coincided with the rapid increase in plasma oLH and testosterone levels, as well as with the oLH-induced stimulation of testicular testosterone and cAMP formation measured in vitro. During the maximum increase in hCG binding, the testosterone response of Leydig cell suspensions to hCG stimulation in vitro was slightly reduced, but the dose-response curve for CAMP production was unchanged. The maximum production rates of testosterone and cAMP were unchanged during the phase of increased receptor binding. Treatment with cytochalasin B, an inhibitor of microfilament function, and with aminoglutethimide, an inhibitor of steroid hormone biosynthesis, abolished the positive effect of oLH on subsequent in vitro [125I]iodo-hCG binding. However, colchicine, a microtubule inhibitor, had no effect on the positive receptor regulation by oLH. These findings demonstrate that the transient increase in LH binding that accompanies the testosterone and cAMP responses to LH is dependent on intact microfilament function and steroidogenesis. The short time course of the increased binding simultaneous increase of both LH and lactogen receptors suggest that the phenomenon may be related to LH-induced changes in cell membrane conformation. Such changes could lead to extension of the plasma membrane with exposure of cryptic receptor sites on the surface of hormone-stimulated Leydig cells.