α1 adrenergic regulation of estrogen-induced increases in luteinizing hormone-releasing hormone mRNA levels and release

Abstract

Prazosin, an α 1 adrenergic antagonist, was used to examine the relationship between adrenergic inputs and the stimulatory effects of estrogen on LHRH mRNA and release. Bilateral cannulae were implanted just dorsal to the preoptic area (POA). Estrous cycles were monitored daily by vaginal smears. On the morning of diestrus, each rat was ovariectomized and assigned to one of three treatment groups: Control — injected with sesame oil ( n = 5); Surge — injected with estradiol benzoate (EB, 10 μg) to produce an LH surge ( n = 5); or, Surge + Prazosin — injected with EB and a prazosin-filled inner cannula was put into the POA ( n = 6). Between 4–6 pm of the following day, rats were anesthetized, decapitated, trunk blood collected, and brains were stored in liquid nitrogen. In situ hybridization was performed using a 32P end-labelled 59-mer complementary to LHRH mRNA. Reduced silver grains, proportional to LHRH mRNA content, were quantified. Treatment with estrogen alone resulted in an LH surge and a 50% increase ( P < 0.05) in numbers of cells expressing LHRH. This estrogen-induced increase and the LH surge were completely blocked ( P < 0.01) by prazosin. Prazosin also decreased ( P < 0.01) the median number of grains per cell from 81 (Surge) to 65 grains per cell (Surge + Prazosin). When the number of grains in LHRH-expressing neurons were totalled, EB increased ( P < 0.05) LHRH gene expression by 53%, and local administration of prazosin completely blocked ( P < 0.01) this increase. Since, coincident with estradiol stimulating the LH surge, it increased potential LHRH synthetic capacity (as measured by LHRH mRNA) and since administration of prazosin into POA blocked the ability of estrogen to do so, it appears that an endogenous α 1 ligand, probably norepinephrine, is a mediator of stimulatory effects of estrogen on LHRH biosynthesis as well as release.