Sexual Differentiation and Feedback Control of Luteinizing Hormone Secretion in the Rhesus Monkey1

Abstract

The inhibitory and stimulatory effects of estradiol-17β(E₂) on systemic luteinizing hormone (LH) levels were studied in three groups of gonadectomized rhesus monkeys: 7 females (F), 7 males (M), and 7 androgenized females (AF). The AF animals, androgenized by exposure to exogenous testosterone in utero, showed masculinization of the external genitalia and behavior after birth. All animals were compared for the short-term inhibitory effects (≤74 h) of E₂ on LH concentrations. Concentrations of 70 to 100 pg/ml of E₂, achieved by sc implantation of a silastic E₂-filled capsule, caused a 40 percent decline in serum concentrations of LH at 6 h; but no significant differences in LH concentrations were found between experimental groups at 6, 24, 48 or 74 h after E₂ treatment. The long-term negative feedback effects of E₂ were studied in 2 trials. In trial 1, at 1 week (but not at 2 or 3 weeks) F treated with small amounts of E₂ (approximately 48 pg/ml, N = 45) had significantly less serum LH compared to preimplant levels (P2 (0.5, 1.5 and 3.0 cm silastic implants) on LH secretion in F, M and AF animals were studied. The 0.5 cm implant of E₂, which sustained a blood level of approximately 22 pg/ml, significantly lowered LH levels in F but not in M or AF. The 3.0 cm capsule, with systemic levels of 100 pg E₂/ml serum, was a significant LH suppressor in all groups. The facilitating actions of estradiol benzoate (EB) in M, F, and AF were compared in two trials with 2 different pretreatment regimens of E₂ (1.5 cm vs 0.5 cm E₂ implant). Under these pretreatment conditions additional exogenous E₂ B produced significant elevations in serum LH over pretreatment levels in all 3 groups in both trials. In the second trial, however, M and AF possessed significantly higher LH levels than F, a result that probably reflects differences in the suppressive effects of low doses of E₂ between F and AF and M. The time course of luteinizing hormone-releasing hormone (LH-RH)-induced LH was studied in the three groups of monkeys, after a 3-week pretreatment with a low dose of E₂ (0.5 cm implant). No significant group differences in pituitary responsiveness were found. These data show that M and AF are less sensitive than F to the long-term feedback inhibition of LH secretion by E₂ and that the EB-induced positive feedback responses are present in all three groups. The similar response pattern observed in males and in females treated with testosterone propionate in utero suggests that the E₂-LH negative feedback control system is sexually differentiated as a function of a hormonal preconditioning in fetal life. "Positive feedback," however, is unaffected unless the higher LH levels in M and AF compared to F after an estrogen challenge are due to factors other than estrogen preconditioning.