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 luteinizing 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 expression of the pituitary gonadotropin subunits. In intact animals, both pituitary and serum levels of LH were similar between these two age groups, while the LHβ mRNA expression was significantly (p < 0.05) greater in young rats. Following OVX in young rats, the serum LH levels markedly increased (p < 0.05) beginning on day 7 and reaching a maximum fourfold increase by day 9. In contrast, the post-OVX increases in serum LH in middle-aged females were significantly delayed. OVX significantly (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 LHβ mRNA expression in both young and middle-aged females, but the levels were significantly (p < 0.05) lower in middle-aged females. Both pituitary and serum levels of FSH were significantly (p < 0.05) higher in middle-aged PE than in young rats prior to OVX, while the FSHβ mRNA expression was similar in both age groups. Following OVX in young rats, serum FSH levels rapidly increased (p < 0.05) on day 3 and attained 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 and marked (five- to tenfold) increases in pituitary FSH contents. After OVX, young rats exhibited an immediate and marked (seven- to tenfold) increase in FSHβ mRNA expression, while middle-aged females showed a similar but a smaller (p < 0.05) magnitude (sixfold) of increase. Alpha mRNA expression showed modest and variable increases in young rats following OVX, while alpha mRNA expression in PE females did not significantly change and was lower (p < 0.01) than that in young rats. These results demonstrate that the post-OVX increases in pituitary gonadotropin secretion were associated with similar changes in the gene expression of the subunits and that delayed and/or attenuated increases in LH and FSH secretion seen in OVX, middle-aged PE females were related to smaller increases in α- and β-subunit mRNA expression. Inasmuch as hypothalamic secretion of gonadotropin-releasing hormone (GnRH) is important in regulating LHP and FSHP mRNA expression, the present findings suggest that altered gonadotropin secretion in aging rats may be related to decreased GnRH release and/or an impaired pituitary mechanism to GnRH stimulation.