Acute and subacute effects of naturally occurring estrogens on luteinizing hormone secretion in the ovariectomized rat: Part 1

Abstract

Acute pretreatment of ovariectomized rats with genistein (G) alters gonadotropin-releasing hormone-(GnRH)-induced LH secretion in a fashion comparable to estradiol (E₂). In the present studies we wished to (A) determine whether G can acutely inhibit tonic LH secretion by oral (po) or intravenous (iv) routes, (B) compare GnRH-induced LH responses following higher iv dose pretreatments with G or E₂, and (C) determine effects of G or E₂ pretreatments on progesterone (P)-induced secretion of LH. Mature Charles River CD rats were ovariectomized, and 2 to 5 weeks later intraatrial cannulae were placed. Serial blood samples were drawn and LH was measured by RIA. In experiments 1 and 2, G or E₂ was administered acutely by gavage or iv, while in experiment 3, G and E₂ were given subcutaneously (sc) in oil 3 days prior to cannulation and sampling. Acute po administration of vehicle or G (0.1, 1.0, and 10 mg/kg BW) had no effect on tonic LH, while E₂ suppressed LH at all doses (0.1, 1.0, and 10 mg/kg BW). Acute iv administration of vehicle and higher doses of G (1 and 10 mg/kg BW) had no effect on tonic LH, while the lowest dose G (0.1 mg/kg BW) and all doses of E₂ (0.1, 1, and 10 mg/kg BW) suppressed tonic LH. In the iv-treated rats, GnRH-induced LH secretion was more profoundly suppressed by G at all doses than by E₂. P (3.2 mg/kg BW) given 3 days after oil (sc) acutely suppressed LH; however, this P-induced suppression was not detected in rats pretreated with E₂ (0.32 mg/kg BW) sc or G (0.32 mg/kg BW and 3.2 mg/kg BW) sc. We conclude that while inhibition of LH secretion by G is limited, G appears to be a more potent inhibitor of GnRH-induced LH secretion than E₂. Additionally, like E₂, G appears to block the suppression of LH by P in this experimental paradigm.