TESTOSTERONE AND POSTNATAL ONTOGENY OF HYPOTHALAMIC-MU ([H-3]DIHYDROMORPHINE) OPIOID RECEPTORS IN THE RAT

Brain opioids modulate the activity of the hypothalamo-pituitary complex by binding to specific receptors which have been subdivided at least into 3 subclasses (mu, kappa, delta, etc). mu-Receptors and their ligands seem to be particularly involved in the control of gonadotropin and prolactin release. It is known that the neuroendocrine system, as well as the brain opioid systems and their receptors, are not fully mature at birth; it is also known that the postnatal maturation of many machineries is under the control of androgens secreted by the developing testes. Consequently, it has been investigated whether the presence or the absence of testosterone at time of birth may induce changes of the binding characteristics of hypothalamic mu-opioid receptors. The experiments have been performed by evaluating the maximal binding capacity (B(max), an index of the number of receptors), and the affinity constant (K(a)) of the specific mu-ligand dihydromorphine in hypothalamic plasma membrane preparations derived from normal male rats, normal female rats, male rats orchidectomized 2 days after birth and female rats treated 2 days after birth with 1.25 mg of testosterone propionate. Animals belonging to the 4 groups were killed at days 16, 26 and 60 of age. The results obtained show that, at 16 days of age, in the 4 groups of rats the number of hypothalamic-mu receptors is identical. At 26 days a significant increase in the number of mu-receptors occurs in normal female animals, while their levels remain similar to those found at 16 days in the other 3 groups of animals. At 60 days of age, the number of mu-receptors in normal females remains elevated, while the number of mu-receptors increases to reach normal female levels in the hypothalamus of neonatally castrated males. At 60 days, there were no changes in normal males or in androgenized females. The variations here reported took place without any change of the K(a) of dihydromorphine for the mu-receptors. These data show a sexual dimorphism of hypothalamic mu-receptors and suggest that their ontogeneitc development may be linked to the presence or the absence of androgens at time of birth.