Ontogeny of Pituitary GnRH Receptors in the Rat

Abstract

Developmental changes in pituitary GnRH receptors were evaluated by longitudinal analysis of GnRH binding sites, and compared with pituitary and serum gonadotropins and serum sex steroid hormones from birth to sexual maturity. In male rats, the pituitary concentration of GnRH receptors increased in early life to a maximum of 260 fmol/mg protein between 15 and 30 days of age, then decreased gradually to reach 65 fmol/mg protein at 60 days of age. However, the total number of pituitary GnRH receptors increased progressively with age and pituitary weight, reaching a plateau of 110 fmol/gland at 40 days of age. These changes in GnRH binding reflect the number of receptor sites rather than altered binding affinity, which remained constant during development (Ka equals 3.3 ± 0.4 × 10⁹ M^-1 in males and 2.6 ± 0.6 × 10⁹ M^-1 in females). The initially high GnRH receptor concentrations in the male were associated with elevated serum LH levels (60 ng/ml) and a peak in serum FSH on day 30. During the pubertal rise in serum testosterone, GnRH receptor concentration showed a reciprocal decline to adult values. In female rats, the highest concentration of GnRH receptors (265 fmol/mg protein) occurred between 15 and 20 days, while the total pituitary GnRH receptor content plateaued earlier than in males at about 25 days of age. The decline in pituitary GnRH receptor concentration occurred 5 days earlier in females than males, corresponding to the earlier fall in serum LH and FSH (about 15–20 days) in females. In both male and female rats, GnRH receptors correlated closely with intrapituitary LH (r equals 0.68 and 0.66 in males and females, respectively). These changes in pituitary GnRH receptors, pituitary LH content, serum gonadotropins, and sex steroids are consistent with a physiological role for GnRH receptors in regulating the activity of the pituitary-gonadal axis during development.