An alpha 1 adrenergic mechanism mediates estradiol stimulation of LHRH mRNA synthesis and estradiol inhibition of POMC mRNA synthesis in the hypothalamus of the prepubertal female rat.
We showed previously that the surge of luteinizing hormone-releasing hormone (LHRH) induced by estradiol-17 beta (E2) in the female rat can be blocked by an alpha 1 adrenergic antagonist. The aim of the present study was to determine whether this was due to a direct action of E2 on noradrenergic projections to LHRH neurons or whether it also involved other systems such as the arcuate pro-opiomelanocortin (POMC) neurons which are thought to inhibit LHRH biosynthesis and release. The experimental preparation was the prepubertal female rat in which an LHRH surge is induced by pregnant mare serum gonadotropin. Prazosin was used as a specific alpha 1 adrenergic antagonist and LHRH and POMC mRNA concentrations and cell numbers, in the medial preoptic area and rostral arcuate nucleus, respectively, were determined by in situ hybridization. Prazosin significantly reduced the total number of LHRH mRNA expressing cells, and increased the total number of POMC mRNA expressing cells and the concentration of POMC mRNA per cell. These results suggest that the inhibition of E2-stimulated LHRH biosynthesis and release by alpha 1 adrenergic blockade may be mediated by two mechanisms; (i) increased POMC synthesis leading to inhibition of LHRH neurons and (ii) direct inhibition of a stimulatory alpha 1 adrenergic/LHRH mechanism.
Rosie
R
R
MRC Brain Metabolism Unit, University Department of Pharmacology, Edinburgh, Scotland.
Sumner
B E
BE
Fink
G
G
D000818:Animals; D004958:Estradiol / Q000502:physiology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D007031:Hypothalamus / Q000378:metabolism*; D017403:In Situ Hybridization; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D011333:Pro-Opiomelanocortin