The Brain Renin‐Angiotensin System and the Regulation of Prolactin Secretion in Female Rats: Influence of Ovarian Hormones

Abstract

This study was designed to investigate the effects of exogenous and endogenous angiotensin II (All) on prolactin release in ovariectomized rats, with and without estrogen and progesterone pretreatment. In the first series of experiments, All or vehicle was injected into the third cerebral ventricle of conscious, freely-moving rats. In both treated and untreated rats, administration of 50 ng All suppressed prolactin levels within 15 min of injection, compared to vehicle-injected rats. In untreated rats, prolactin levels returned to baseline values by 30 min, while in treated rats, prolactin levels remained suppressed for an hour.In the second series of experiments, the involvement of endogenous brain All in tonically suppressing prolactin release was assessed by administering either All receptor blockers (saralasin or sarthran) or an All synthesis inhibitor (enalaprilat, an inhibitor of the conversion of angiotensin I to All). Neither All receptor blockade nor converting enzyme inhibition resulted in any change in prolactin levels in untreated levels in untreated rats. However, following treatment with ovarian steroids, infusion of saralasin or injection of enalaprilat resulted in a significant increase in plasma prolactin titers. During saralasin infusion, prolactin levels were significantly increased by 15 min and continued to be higher than controls at 60 min. After enalaprilat administration, prolactin levels did not rise significantly until 90 min and then remained elevated up to 120 min post-injection. These latter results suggest that at least one h is required for maximal inhibition of angiotensin synthesis in the brain.These data demonstrate that low doses of All suppressed basal prolactin secretion in both untreated and ovarian steroid-treated, ovariectomized rats. However, treated rats appeared to be more sensitive than untreated animals to the prolactin-lowering effects of centrally administered All. The lack of prolactin response in untreated rats when brain All synthesis was inhibited or All receptors were blocked suggests that, in the absence of ovarian steroids, endogenous All was not acting tonically to suppress prolactin secretion. Following exposure to ovarian steroids, however, the endogenous brain All system appeared to be activated and involved in controlling prolactin release.The anterior pituitary gland hormone, prolactin, i s involved in lactation, ovarian and mammillary gland function, pseudopregnancy in female rats, and i s released in response to stress (1). In human males and females, hyperprolactinemia i s associated with impaired sexual behavior and functioning, as well as infertility (2).Prolactin secretion is mainly under tonic inhibitory control by dopamine, derived from the brain tuberoinfundibular system (3). On the other hand, a variety o f peptides (e.g. vasoactive intestinal peptide, thyrotropin-releasing hormone) including angiotensin I1 (AII), have been identified as putative prolactin-releasing factors when applied directly to the anterior pituitary gland (4). Und...

Angiotensin II AT1AReceptor mRNA Expression Is Induced by Estrogen–Progesterone in Dopaminergic Neurons of the Female Rat Arcuate Nucleus

“…Higher numbers of AT 1 receptors could possibly magnif y the effect of endogenous Ang II. This may explain the enhancement of the estrogen /progesterone-caused inhibition of prolactin release by intraventricular injection of Ang II (Myers and Steele, 1989). Progesterone increases the secretion of dopamine into the hypophyseal portal blood (Cramer et al, 1979), an effect that could be mediated via a regulation of the number of AT 1 receptors in the dorsomedial arcuate nucleus.…”

“…In accordance with this observation, Myers and Steele (1991) found no effect of centrally injected Ang II receptor antagonists on prolactin levels in male rats. Because this is also the case in untreated OV X rats (Myers and Steele, 1989), it is possible that endogenous Ang II affects prolactin release only under certain conditions like estrogen treatment. Indeed, during restraint stress in male rats, when prolactin levels are increased, blocking of central Ang II receptors f urther arguments the prolactin increase (Myers and Steele, 1991).…”

“…In the brain, Ang II has indirect inhibitory control of prolactin release. Brain Ang II may f unction to limit the magnitude of the prolactin secretion under certain conditions, such as after concurrent estrogen/progesterone administration to OVX rats (Myers and Steele, 1989) or after stress in male rats (Myers and Steele, 1991). This indirect inhibitory effect of Ang II probably is attributable to its stimulation of dopamine release, the predominant inhibitor of prolactin secretion (Steele et al, 1982;Inoue and Negro-Vilar, 1989).…”

Estrogens Regulate Angiotensin-Converting Enzyme and Angiotensin Receptors in Female Rat Anterior Pituitary

“…The inhibitory effect of estrogen on the expres sion of the number of AT receptors in the anterior pitu itary is not accompanied by a decrease in AT-stimulated prolactin secretion, indicating that estrogen modulation of postreceptor events could be the predominant deter minant of lactotroph responsiveness during stimulation of prolactin release [36,44], Intravenous administration of AT inhibitors docs not affect the timing or magnitude of the prolactin surge during proestrus [4], However, es trogen (and progesterone) enhance the prolactin lowering effect of AT when injected intracerebrally [45], and this mechanism may be mediated by the central ner vous system. A role of estrogen in the central effects of AT on pituitary control has been described earlier [46].…”

Les récepteurs de l'angiotensine II dans le placenta humain sont de type AT1

“…En outre, il a été démontré que l'angiotensine Il stimule la sécrétion de l'hormone placentaire lactogène (hPL) par des cellules trophoblastiques , la sécrétion de la prolactine par des cellules adénohypophysaires (Platia et al, 1986;Myers et Steele, 1989) et la biosynthèse des hormones stéroïdes par les cellules de la granulosa (Pucell et al, 1987;Guichard et al, 1988;Palumbo et al, 1989 (Cooke et al, 1981;Wilkes et al, 1985;Kurauchi et al, 1990 (Munson et Rodbard, 1980;Whitebread et al, 1989) (Whitebread et al, 1989).…”