Sexually dimorphic ontogeny of GABAergic influences on periventricular somatostatin neurons

The biosynthesis and secretion of somatostatin (SRIH) within the hypothalam ic periventricular-median eminence (PeN-ME) pathway follows a sexually diff erentiated developmental pattern beginning in the early neonatal period. It is generally accepted that testosterone plays a role in these processes, b ut the mechanisms underlying the age and sex differences are poorly underst ood. The present study sought to investigate the hypothesis that gamma-amin obutyric acid (GABA) may play a role in determining sex differences in SRIH neuronal activity. Using an in vitro hypothalamic preparation where more t han 97% of the immunoreactive SRIH is contained within the PeN-ME pathway, peptide release in response to the GABA(A) receptor antagonist, bicuculline , was followed through development. In the male a stimulatory response, ind icative of an inhibitory GABAergic tone on SRIH secretion, was observed as early as postnatal day (P) 5. This persisted throughout juvenile developmen t (P10, P17) and was present also in the adult male (P75), but in the perip ubertal period the response to bicuculline was first lost (P25) and then re versed to an inhibition (P40), suggesting a transient switch to an apparent stimulatory GABAergic tone on SRIH release. By contrast, in the female, no bicuculline responsiveness was seen until P25 when it caused a decrease in SRIH release which persisted into adulthood. Using in situ hybridization s tudies we found no evidence to support the view that these age- and sex-dep endent differences were due to changes in the expression of GABA(A) recepto r alpha-subunits (alpha(1) and alpha(2)) which are colocalised in the PeN S RIH neurons. Following adult gonadectomy, the bicuculline response was abol ished in the male, whereas, in the female it was reversed and identical in magnitude to the response in the intact male. These results demonstrate mar ked sex differences in GABA(A)-receptor-mediated influences on SRIH release which develop soon after birth and, in the adult, depend on gonadal factor s. In the male these factors activate a primarily inhibitory influence, whe reas in the female they facilitate an apparently stimulatory tone of GABA o n SRIH secretion via the GABA(A) receptor. Our findings thus support the vi ew that GABAergic transmission may play a key role in generating sex differ ences in the mode of SRIH secretion from the hypothalamus which has been sh own to be a major factor in determining the sexually dimorphic patterns of growth hormone secretion. (C) Copyright 1999 S. Karger AG, Basel.