Receptors for chorionic gonadotropin in the corpus luteum of the rhesus monkey during simulated early pregnancy: Lack of down-regulation

Stimulation of the primate corpus luteum (CL) by endogenous CG in early pregnancy or by exogenous hCG in simulated early pregnancy is transient, possibly due to a drop in the number of available gonadotropin receptors in the CL. The objective of the current study was to determine if this reduction in available CG receptors in the CL is due to down-regulation of the total receptor population or occupation of receptors by CG. CL were removed from rhesus monkeys (n = 27) during prolonged CG exposure in simulated early pregnancy. Luteal tissue was homogenized, and a particulate preparation (20,000 g) was formed. Bound gonadotropin was eluted from half of each tissue preparation with 0.05 m Na acetate-HCl in 0.1% gelatin (pH 3.3); the other half was treated with control buffer (0.05 m Tris-HCl, pH7.4). The hCG in the eluate was quantified by RIA and used to estimate the number of occupied receptors. Numbers and affinities of receptors were estimated by Scatchard analyses of specific [¹²⁵I]hCG binding. Serum concentrations of progesterone increased within 9 h of hCG treatment and declined between 3 and 10 days of treatment. Whereas the number of available receptors declined from 0 h to 10 days of hCG treatment, the number of receptors occupied by hCG increased throughout treatment from 0.19 ± 0.01 fmol/mg tissue (mean ± se) after 2 h of treatment to 7.76 ± 1.73 fmol/mg after 10 days of treatment (P < 0.05). The total number of receptors (available plus occupied) did not change throughout the 10-day treatment period (11.93 ± 2.11 fmol/mg at 0 h vs. 9.64 ± 1.86 at 10 days; P > 0.10). The dissociation constants (K_d) for CG binding were greater (P < 0.05) after 6 days (4.10 ± 0.57 × 10⁻¹⁰ m) and 10 days (5.24 ± 0.54 × 10⁻¹⁰ m) of treatment than after 0–3 days (0.95 ± 0.06 × 10⁻¹⁰ m) of treatment. Notably, the percentage of total receptors able to rebind hCG after elution declined from 0 h (79.0 ± 5.4%) to 10 days (23.0 ± 3.2%; P < 0.05). Rebindability was highly correlated with the number of available (r = 0.906; P < 0.05) and occupied (r = -0.999; P < 0.01) CG receptors. Thus, the reduction in available gonadotropin-binding sites in the CL during simulated early pregnancy is largely due to occupancy rather than down-regulation of receptors. Although the decrease in the ability of the receptors to rebind hCG after elution suggests a change in the nature of the receptor, these data reflect a remarkable constancy of total numbers of gonadotropin receptors amidst marked changes in circulating CG and luteal function during simulated early pregnancy.