STIMULATION OF HYPOTHALAMIC PROLACTIN-RELEASE BY VERATRIDINE AND ANGIOTENSIN-II IN THE FEMALE RAT - EFFECT OF OVARIECTOMY AND ESTRADIOL ADMINISTRATION

In the female rat immunoreactive prolactin (IR-PRL) has been identified in the hypothalamus and in other brain regions. Brain IR-PRL is not of pituitary origin and, based on polyacrylamide gel electrophoresis and peptide mapping, shares a high degree of sequence homology with its pituitary counterpart. We have previously shown that hypothalamic tissue can release IR-PRL in vitro when depolarized by potassium. In this study, we examined the release of IR-PRL from hypothalami obtained from intact and ovariectomized rats and incubated in the presence of veratridine (an alkaloid which depolarizes excitable membranes), angiotensin II, or thyrotropin-releasing hormone. Hypothalamic tissue spontaneously released IR-PRL, and this release was significantly increased by veratridine or angiotensin II in a dose-dependent manner. The specificity of the angiotensin-II-evoked IR-PRL release was demonstrated by the inhibitory effect of saralasin, an angiotensin II receptor antagonist, on hypothalamic IR-PRL release. Thyrotropin-releasing hormone (100-mu-M) had no effect on hypothalamic IR-PRL release. Ovariectomy decreased hypothalamic IR-PRL content and IR-PRL release in response to veratridine and angiotensin II. The effect of estradiol on hypothalamic IR-PRL content and release was also examined by obtaining hypothalami from ovariectomized rats injected with estradiol (1-mu-g/day) or vehicle for 5 days. When compared with vehicle injected rats, administration of estradiol significantly increased the hypothalamic IR-PRL content (46 +/- 4 vs. 81 +/- 16 ng/mg protein). In the same rats, the veratridine (100 mM; 7.26 +/- 0.97 vs. 10.4 +/- 1.46 ng/ml) and angiotensin II (1-mu-M; 5.08 +/- 0.84 vs. 9.9 +/- 1.2 ng/ml) stimulated IR-PRL release was significantly increased when compared with vehicle-injected rats. These data indicate that angiotensin II, but not thyrotropin-releasing hormone, stimulates the release of IR-PRL from the female hypothalamus. The increase in hypothalamic IR-PRL content and release by estradiol suggests that estradiol stimulates the hypothalamic IR-PRL synthesis, resulting in an increase in the releasable pool of IR-PRL.