Effects of a Norethynodrel-Mestranol Combination (Enovid) on Hypothalamic and Pituitary Hormones in Rats1

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Abstract
The effects of a norethynodrel-mestranol combination (Enovid) were determined on the hypothalamic content of luteinizing hormone-releasing factor (LRF), follicle stimulating hormone-releasing factor (FSH-RF) and prolactin inhibiting factor (PIF) in mature female rats. Its effects were also observed on pituitary concentration of LH [luteinizing hormone], FSH [follicle stimulating hormone] and prolactin, and on the ovaries, mammary glands and other tissues. Enovid injected subcutaneously once daily at a dose of 200 ug/100 g body weight for -0 days resulted in decreased pituitary FSH and LH and increased prolactin concentration. In vitro assays of neutralized acid extracts of hypothalamus from Enovid-injected rats revealed that it significantly decreased FSH-RF, LRF and PIF content when compared with control rats. The ovaries of Enovid-injected rats were smaller than in control rats, follicular development was inhibited, and large corpora lutea were present despite indications that ovulation was inhibited. Enovid also stimulated extensive lobulo-alveolar growth and secretion in the mammary glands of intact animals, and increased the weights of the anterior pituitary, uterus and adrenals. Enovid had no effect on the ovaries or mammary glands of hypophysectomized rats. These corresponding effects of Enovid on the hypothalamus, pituitary, ovaries and mammary glands suggest that the hypothalamus was probably the major site of Enovid action, and that its predominant actions were estrogenic in nature.