EVIDENCE FOR THE INVOLVEMENT OF CORTICOTROPIN-RELEASING FACTOR IN THE INHIBITION OF GONADOTROPIN-RELEASE INDUCED BY HYPERPROLACTINEMIA

The hypothesis was tested that corticotropin-releasing factor (CRF) is involved in the inhibition of gonadotropin secretion during chronic hyperprolactinemia. Two models of hyperprolactinemia were used, namely inoculation with the prolactin (PRL)-secreting tumor 7315b and implantation of isogenic pituitary glands. Gonadectomized, adrenalectomized male rats received a testosterone capsule and a corticosterone pellet and were inoculated subcutaneously with tumor 7315b. Similar rats without tumor served as controls. The rats were studied 3-4 weeks later while anesthetized with urethane. Plasma testosterone and corticosterone were similar in the two groups of rats. Compared to controls, the tumor-bearing rats had significantly higher plasma levels of PRL (100-fold increase) and adrenocorticotropin (ACTH; 3-fold increase), whereas plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) had significantly decreased to 15 and 40%, respectively. CRF release into hypophysial stalk plasma was higher in rats with tumor 7315b than in controls (298 ± 23 vs. 197 ± 28 pg/h), and hypothalamic CRF content had increased from 3.0 ± 0.3 to 4.3 ± 0.3 ng. Male rats received 3 pituitary glands under the kidney capsule. Sham-operated rats served as controls. They were studied 5-7 weeks later while anesthetized with urethane. Compared to controls, pituitary-grafted rats had larger adrenals (49 ± 4 vs. 34 ± 2 mg), higher plasma PRL (156 ± 18 vs. 52 ± 8 ng/ml), ACTH (0.46 ± 0.05 vs. 0.22 ± 0.02 ng/ml) and corticosterone (455 ± 39 vs. 268 ± 14 ng/ml), and lower plasma levels of LH (21 ± 2 vs. 41 ± 6 ng/ml). Plasma FSH and testosterone, and hypothalamic CRF content were similar in both groups of rats. CRF release into hypophysial stalk plasma was somewhat, but not significantly, higher in pituitary-grafted rats than in control rats (102 ± 32 vs. 82 ± 37 pg/h). Thus, both models of chronic hyperprolactinemia seem to activate the hypothalamic-adenohypophysial-adrenal axis. It is suggested that at least part of the action of PRL is due to an activation of CRF-containing neurons, which causes inhibition of hypothalamic LH-releasing hormone secretion and consequently pituitary gonadotropin release. © 1990 S. Karger AG, Basel.