C. P. Fawcett

Effects of Estrogen on Plasma and Pituitary Gonadotropins and Prolactin, and on Hypothalamic Releasing and Inhibiting Factors

Single subcutaneous injections of varying doses of estradiol benzoate (0.2–5 µg) in ovariectomized female rats were capable of lowering plasma FSH and LH and elevating plasma prolactin as determined by radioimmunoassay. The effects were demonstrable by 24 h and more marked at 48 h. Once an effect had been obtained, there was no clearly increased effect of higher doses of steroid. Pituitary content of FSH, LH, and prolactin increased significantly at 48 h with the 5 µg doses of estrogen, accompanied by an increase in anterior pituitary weight. Hypothalamic content of FSH-releasing factor (FRF) was reduced at 48 h only by the 1 µg dose of estradiol, whereas the content of LH-releasing factor (LRF) declined at 48 h only with the 0.2 and 0.5 µg doses. Prolactin-inhibiting factor (PIF) declined at 24 h after 0.5, 1, or 5 µg of estradiol and the level was still low at 48 h in the case of the 1 or 5 µg doses. The results are interpreted to mean that single injections of estradiol can inhibit release and synthesis of FSH and LH at least in part by a hypothalamic mechanism. With high doses, an elevation in stored hormone results in the pituitary, since synthesis of hormone is inhibited less than release. On the other hand, estrogen increases release and synthesis of prolactin and this effect is achieved, at least in part, by altered hypothalamic function.

Inhibitory and Facilitatory Effects of Estradiol 17β on Pituitary Responsiveness to a Luteinizing Hormone-Follicle Stimulating Hormone Releasing Factor (LH-RF/FSH-RF) Preparation in the Ovariectomized Rat

Summary A single intravenous injection of 200 ng of estradiol significantly depressed both LH release in vivo for up to 9 hr and unstimulated LH and FSH release in vitro at 3 hr. The releasing factor preparation evoked significantly less LH release in vivo at 3 hr after estradiol than in saline-injected controls; however, by 6–9 hr after estradiol, the response to LH-RF/FSH-RF stimulation was noticeably enhanced for both LH and FSH release in vitro and in vivo when compared to the response in the ovariectomized controls, even though plasma LH was still suppressed. It is concluded that subsequent to an initial suppression of gonadotroph sensitivity to LH-RF/FSH-RF stimulation, there is an augmented hypophyseal responsiveness to the releasing factor following estrogen treatment.

The effect of colchicine on the release of rat anterior pituitary hormones in vitro.

Summary 1. Colchicine significantly increased the basal rate of release of growth hormone while it did not effect the basal rate of release of LH, FSH or TSH from anterior pituitaries incubated in vitro. 2. Colchicine significantly enhanced the action of LRF and FRF by increasing the rate of release of LH and FSH. This effect was magnified by preincubating the pituitaries in colchicine for 2 hr. 3. Colchicine at 1 × 10-3 M significantly potentiated potassium-stimulated LH and FSH release only when the colchicine-treated glands were preincubated with the drug for 2 hr prior to incubation.

The effect of median eminence (ME) lesions on plasma levels of FSH, LH, and prolactin in the rat.

Summary Lesions were located in the ME of ovariectomized rats to determine their effect on plasma levels of FSH, LH, and prolactin as determined by RIA. Initial levels of FSH and LH were elevated as a result of removal of steroid feedback from the ovaries. One week after placement of lesions plasma LH levels had fallen, 32-fold, to very low values. There was a lesser, 3-fold, fall in FSH, and a dramatic, 15-fold, rise in prolactin to levels nearly as high as those observed in lactating rats and in females in proestrus. In sham-operated controls, in which the electrodes were lowered into the hypothalamus stopping short of the ME, no significant changes were seen in the plasma levels of all three hormones. The results demonstrate that the release of LH and to a lesser extent FSH is decreased after removal of hypothalamic control, whereas the release of prolactin is greatly enhanced.

Plasma gonadotropins and prolactin in pseudopregnancy in the rat.

Summary 1. Cervical probing of estrous rats resulted in an elevation of plasma prolactin 15 min later. 2. Plasma prolactin was not elevated on day 4 of pseudopregnancy and was actually lower on day 9 than in diestrous controls. 3. On day 4 of pseudopregnancy plasma LH levels were lower than those observed in the controls; where FSH levels were elevated on day 4 and 9. 4. Following castration on day 4 of pseudopregnancy, plasma FSH and LH levels both rose, but plasma LH rose to a higher value in the pseudopregnant castrates than in controls on the 5th day after spaying. Prolactin levels remained unchanged following spaying. 5. It is concluded that the discharge of prolactin which initiates pseudopregnancy in the rat is not maintained throughout pseudopregnancy and is associated with a suppression of LH and an augmentation of FSH release from the pituitary.