Alterations in plasma and ovarian immunoreactive inhibin during reproductive aging in the female rat

Previously, we showed that ovarian inhibin α- and β;(A)-subunit mRNAs are elevated in middle-aged and old persistent-estrous (PE) female rats. To determine whether higher inhibin subunit mRNA expressions result in increased circulating inhibins during reproductive aging, plasma immunoreactive inhibin α (ir-inh α) and gonadotropins were measured in young, middle-aged and PE rats. Plasma LH profiles were distinctly divergent in the middle-aged rats with some showing LH surges indistinguishable from young rats and others showing significantly attenuated LH surges. Plasma ir-inh α in middle-aged rats with LH surges were similar to those of young rats. However, animals with attenuated LH surges had higher peak ir-inh α levels than young and middle-aged animals with LH surges. Immunohistochemistry revealed increased levels of ovarian inhibin α staining in those animals with attenuated LH surges. Overall, the highest plasma and ovarian inhibin α were found in PE rats which lack LH surges. However, significant decreases of plasma and ovarian inhibin α were seen after reinstatement of estrous cyclicity with progesterone implant treatment. Thus, increases in both plasma and ovarian inhibin α appear to be closely associated with attenuation or loss of the preovulatory gonadotropin surge that occurs during aging.