ALTERATIONS IN THE POSTOVARIECTOMY INCREASES IN GONADOTROPIN-SECRETION IN MIDDLE-AGED PERSISTENT-ESTROUS RATS - CORRELATION WITH PITUITARY GONADOTROPIN SUBUNIT GENE-EXPRESSION

This study compared the changes in pituitary and serum levels of lutei nizing hormone (LH) and follicle-stimulating hormone (FSH) at various times following ovariectomy (OVX) between young cyclic and middle-aged persistent-estrous (PE) rats and related these to the relative gene e xpression of the pituitary gonadotropin subunits. In intact animals, b oth pituitary and serum levels of LH were similar between these two ag e groups, while the LHbeta mRNA expression was significantly (p < 0.05 ) greater in young rats. Following OVX in young rats, the serum LH lev els markedly increased (p < 0.05) beginning on day 7 and reaching a ma ximum fourfold increase by day 9. In contrast, the post-OVX increases in serum LH in middle-aged females were significantly delayed. OVX sig nificantly (p < 0.05) increased pituitary LH contents of young rats by day 5, but had no effect on LH contents in middle-aged females until day 30 post-OVX. These changes were associated with increases in LHbet a mRNA expression in both young and middle-aged females, but the level s were significantly (p < 0.05) lower in middle-aged females. Both pit uitary and serum levels of FSH were significantly (p < 0.05) higher in middle-aged PE than in young rats prior to OVX, while the FSHbeta mRN A expression was similar in both age groups. Following OVX in young ra ts, serum FSH levels rapidly increased (p < 0.05) on day 3 and attaine d tenfold higher values by day 30. In middle-aged PE females, OVX also produced a similar pattern of changes in serum FSH as in young rats, but the levels were significantly (p < 0.05) lower than those of young rats. Following OVX, both young and middle-aged rats showed similar a nd marked (five- to tenfold) increases in pituitary FSH contents. Afte r OVX, young rats exhibited an immediate and marked (seven- to tenfold ) increase in FSHbeta mRNA expression, while middle-aged females showe d a similar but a smaller (p < 0.05) magnitude (sixfold) of increase. Alpha mRNA expression showed modest and variable increases in young ra ts following OVX, while alpha mRNA expression in PE females did not si gnificantly change and was lower (p < 0.01) than that in young rats. T hese results demonstrate that the post-OVX increases in pituitary gona dotropin secretion were associated with similar changes in the gene ex pression of the subunits and that delayed and/or attenuated increases in LH and FSH secretion seen in OVX, middle-aged PE females were relat ed to smaller increases in alpha- and beta-subunit mRNA expression. In asmuch as hypothalamic secretion of gonadotropin-releasing hormone (Gn RH) is important in regulating LHbeta and FSHbeta mRNA expression, the present findings suggest that altered gonadotropin secretion in aging rats may be related to decreased GnRH release and/or an impaired pitu itary mechanism to GnRH stimulation.