Ultrastructural changes in gonadotropin-releasing hormone neurons as a function of age and ovariectomy in rats

Abstract

In this study we examined the effects of aging on various aspects of the ultrastructure of gonadotropin-releasing hormone neurons in female rats, including the density of synaptic input and the volume fraction of various subcellular organelles. In addition, we explored the possibility that removal of estrogen might provide a protective effect on the aging of the gonadotropin-releasing hormone neuron as exposure to gonadal steroids alters the time course of reproductive aging. Our experimental groups included four- and 18–20-month-old virgin female rats divided as follows: young intact, young short-term ovariectomized, old intact, old short-term ovariectomized and old long-term ovariectomized. Brain tissue was processed for immunocytochemical detection of gonadotropinreleasing hormone neurons and selected cells from the preoptic area were chosen for electron microscopic examination. The percentage of plasma membrane containing synaptic modification was quantified using a morphometrics program, and the volume fraction of lysosomes/lipofuscin, rough endoplasmic reticulum and Golgi apparatus were estimated using point count stereology. Whereas we had previously found a significant increase in the density of synaptic input to gonadotropinreleasing hormone neurons in aged virgin male rats, the density of synaptic input to gonadotropin-releasing hormone cells in the virgin female was not affected by age. The volume fraction of lysosomes/lipofuscin was increased in all age groups. Aging produced a dramatic decrease in the volume fraction of rough endoplasmic reticulum as well as a decrease in Golgi, suggesting a general decrease in biosynthetic activity of the cells. There was no apparent protective effect of long-term reduction in exposure to estrogen over the life span on these aging changes. Ovariectomy had paradoxical effects depending on the age of the animal: there was a decrease of the rough endoplasmic reticulum in the young rat and an increase in the old animal. We also noted that ovariectomy did not result in hypertrophied glial ensheathment of gonadotropin-releasing hormone neurons in female rats as we had observed in the Rhesus macaque. We conclude that aging changes in the gonadotropin-releasing hormone system are affected by factors related to the sex and hormonal condition of the animal.