Ovarian steroid regulation of glutamic Acid decarboxylase gene expression in individual hypothalamic nuclei.
Abstract The possibility that steroids exert their effects on luteinizing hormone (LH) and prolactin release and female sexual behaviour via altering gamma-aminobutyric acid (GABA) synthesis within the hypothalamus was investigated. Ovariectomized rats were treated with either oil, 5 mug oestradiol benzoate (OB) or 5 mug OB plus 0.5 mg progesterone (P) 48 h later; autopsy was carried out 54 h after the OB injection. At this time, both steroid treatments stimulated prolactin release and lordotic activity. OB alone exerted a negative feedback effect on LH release while OB plus P stimulated an LH surge. The brains of the rats in these three treatment groups were microdissected and glutamic acid decarboxylase messenger nbonucleic acid (GAD mRNA) was estimated in specific hypothalamic areas obtained from individual brains; these areas included the preoptic area (POA), ventromedial nucleus (VMN), anterior medial portion of the zona incerta (Zl) and the arcuatemedian eminence area (ARC/ME). GAD mRNA concentrations were assessed by the slot-blotting technique and expressed as a ratio of GAD mRNA: beta-actin mRNA. Both steroid treatments significantly reduced GAD mRNA in the ARC/ME and Zl and OB plus P also reduced the concentration in the POA, while OB alone had no effect in this area. Neither treatment affected GAD mRNA in the VMN. These results indicate that when steroids stimulate LH and prolactin release and female sexual behaviour, they reduce GABA activity probably by reducing GABA synthesis in the POA, Zl and ARC/ME. This suggests that GABA normally has an inhibitory influence on these parameters. GABA synthesis does not however, appear to be involved in the negative feedback effects of steroids on LH release as measured 54 h after OB treatment.
Leigh
A J
AJ
Tne Molecular Endocrinology Group, London SW17 ORE, UK.
Carter
N D
ND
Horton
R
R
Silverligh
J J
JJ
Wilson
C A
CA