Evidence for the Involvement of Corticotropin-Releasing Factor in the Inhibition of Gonadotropin Release Induced by Hyperprolactinemia

Abstract

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.