Effects of a Single Injection of Estradiol Valerate on the Hypothalamic Arcuate Nucleus and on Reproductive Function in the Female Rat*

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Abstract
Young adult cyclic female rats were each injected with 2 mg estradiol valerate (EV) in sesame oil. Controls received an equivalent volume of sesame oil. Within 2 mo. after injection, most of the EV-treated animals showed persistent vaginal estrus and small polyfollicular ovaries as well as pathological changes in the hypothalamic arcuate nucleus. This pathological process was gradually progressive such that by 6 mo. after EV injection, the basal lateral region of the nucleus contained numerous reactive microglia, astrocytes and degenerating elements of the neuropil. Experimental rats had elevated plasma PRL [prolactin] and GH [growth hormone] concentrations which gradually diminished. Plasma estradiol concentration remained elevated 2 mo. after injection, while plasma LH [luteininzing hormone] and FSH [follicle stimulating hormone] concentrations stayed within the high and low normal range, respectively. Pituitary glands of injected animals weighed significantly more than those of controls 5.5 mo. after injection, but the enlarged glands did not cause hypothalamic compression. As mechanical anterior deafferentation of the medial basal hypothalamus was previously shown to produce similar endocrine and reporductive alterations, estradiol treatment may result in a functional-anatomical disconnection of the arcuate nucleus from the more anterior hypothalamic areas that regulate cyclicity. Whether this type of functional-anatomical phenomenon underlies other varieties of induced or secondary acyclicity in females remains to be determined.