Gonadotropin Receptors in Rat Ovarian Tissue: III. Binding Sites for Luteinizing Hormone and Differentiation of Granulosa Cells to Luteal Cells1

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Abstract
A pseudopregnant, immature rat model for studying hormone-receptor interactions and biochemical mechanisms involved in the differentiation of granulosa cells to luteal cells was developed and characterized. Pseudopregnancy was induced by sequential treatment of 25 day old intact rats for 2 days with ovine follicle stimulating hormone (FSH; 5 injections, each equivalent to 250 .mu.g of NIH[National Institute of Health]-FSH-S1), followed by a single injection of ovine luteinizing hormone (LH; equivalent to 120 .mu.g NIH-LH-S1) at 1600 h day 27. The FSH-treatment initiated follicular development and the appearance in expressed granulosa cells of LH-receptor (quantified by binding of human [125I]iodo-CG [chorionic gonadotropin]). Subsequent LH-induced luteinization of these granulosa cells was associated with a further increase in LH-receptor as determined by binding studies in vitro and uptake studies in vivo. Serum progesterone concentrations increased transiently following the injection of LH, rose steadily in association with the increase in LH-receptor in luteinizing granulosa cells, reached the highest levels on days 31 and 32, remained elevated through day 37, then fell in association with a decline in LH-receptor at the end of pseudopregnancy (day 39). Serum concentrations of LH, and to a lesser extent, prolactin, began to rise prior to the injection of LH during the afternoon on day 27. The exogenous LH caused a further increase in endogenous prolactin during the afternoon and evening of day 27, and caused some elevation of prolactin on day 29. Autoradiograms, prepared on sections of ovaries fixed 2 h after the i.v. injection of human [125I]iodo-CG at various times during the pseudopregnancy, indicated that the LH-receptor appeared first in the peripheral granulosa cells of large Graafian follicles, and then increased centripetally. The concentration of available LH-receptor may be closely related to the stage of differentiation of granulosa to luteal cell development and the associated changes in granulosa-luteal cell function.