Short-term inhibition of macromolecular synthesis and androgen-induced sexual differentiation of the rat brain

Abstract

A single injection of 100 μg testosterone propionate (TP) to 5-day-old female rats results in irreversible changes in the development of brain centres regulating gonadotrophin release. The dependence of this process on protein and DNA synthesis during a short period (1–24 h) after injection of TP was studied. Hypothalamic protein synthesis was arrested for a period of up to 6 h after injection of TP by the administration of puromycin (20 μg) or cycloheximide (3 μg) directly into the brain. Inhibition of DNA synthesis in the hypothalamus for up to 24 h after injection of TP was accomplished by injections of hydroxyurea (1 mg) or 5-bromodeoxyuridine (50 μg) into the brain. Neither the blockade of protein synthesis nor that of DNA synthesis in the hypothalamus prevented the action of TP as judged by the development of the persistent oestrus syndrome. Hence, if the induction of androgenization by TP is dependent on macromolecular synthesis in the hypothalamus, this inductive phase must be of longer duration than has been suggested in the literature.