Gonadotropin Receptors of the Primate Corpus Luteum. II. Changes in Available Luteinizing Hormone- and Chorionic Gonadotropin-Binding Sites in Macaque Luteal Membranes during the Nonfertile Menstrual Cycle*

Abstract

The gonadotropin receptor population of the primate corpus luteum was examined at specific stages of the nonfertile menstrual cycle via [¹²⁵I]iodohuman LH ([^I25I]iodohLH)/ hCG binding to 15,000 × g particulate fractions of luteal tissue obtained from rhesus monkeys 2, 4-5, 6-9, 10-12, 13-15, and 16-18 days after the midcycle LH surge. The number (maximum binding capacity) and affinity (dissociation constant) of available LH-CG receptors were determined from Scatchard analyses of equilibrium binding data. Available receptors displayed comparable affinity for both hLH and hCG throughout the lifespan of the corpus luteum (dissociation constant, 0.88± 0.04 × 10,^-10 and 0.79 ± 0.03 × 10^-10 M, respectively). In contrast, the number of receptors increased from the early luteal phase to maximal levels (8.9 7± 0.75 fmol LH bound/mg tissue) during the midluteal phase (6-9 days post-LH surge) of the cycle. Luteal weight and se um progesterone content reached maximal levels 4-5 days after the LH surge, before the development of maximal LH binding capacity. Receptor number decreased significantly (4.9 ± 0.6 fmol LH/mg; P < 0.05) by 13ndash15 days after the LH surge and dropped to low but detectable levels around menses (2.3 ± 0.3 fmol LH/mg). Although progesterone levels were declining in four of eight monkeys luteectomized 10–12 days after the LH surge, the LH binding capacity of these four tissues (9.0 ± 2.4 fmol/mg) was comparable to that of tissues removed while progesterone remained elevated (8.7 ± 0.8 fmol/mg). Thus, the decline in LH binding capacity preceded any loss in luteal weight, but appeared to follow the early decline in circulating progesterone at luteolysis. Similar changes in hCG binding capacity also occurred throughout the lifespan of the corpus luteum. Coincubation of luteal particulate fractions with 10^-8 M prostaglandin F₂α signifi antly (P < 0.01) inhibited [^l25I]iodohLH uptake, whereas 10^-8 M prostaglandin E₂ and estradiol had no effect. The data indicate that marked changes in the number, but not the affinity, of available LH-CG receptors are associated with the development and regression of the corpus luteum of the rhesus monkey during the menstrual cycle. However, the initial stages of luteolysis, as judged from declining serum progesterone levels, are not necessarily preceded by or associated with an appreciable decline in available LH-CG receptors. Although potential luteolytic agents may directly modulate LH-CG receptor availability in vitro, the loss of luteal LH receptors is not an obligatory step in the normal induction of luteolysis in the menstrual cycle.