The Effect of Transient Dopamine Antagonism on Thyrotropin-Releasing Hormone-Induced Prolactin Release in Ovariectomized Rats Treated with Estradiol and/or Progesterone*

Abstract

PRL release was studied in ovariectomized (OVX) rats pretreated with estradiol benzoate (EB), progesterone (P), or a combination of both steroids using a protocol that was selected to mimic ovarian steroid changes that have been observed during the female rat 4-day estrous cycle and early pregnancy. On the morning of the experiment, the animals received injections of either the dopamine (DA) antagonist domperidone (0.01 mg/rat iv) or vehicle (acetic acid in saline). Five minutes later, all animals received injections of the DA agonist 2-bromo-alpha-ergocryptine (CB-154; 0.5 mg/rat, iv) followed 60 min later by the administration of TRH (1.0 microgram/rat, iv). Plasma obtained from blood samples taken during the experiment was assayed for PRL by RIA. In OVX or P-treated OVX rats, a transient blockade of DA by domperidone did not alter the sensitivity of the pituitary to TRH administration, as measured by an increase in plasma PRL. However, such an effect of DA blockade was induced by 2 days of EB treatment and was maintained and amplified by P administration after EB injections. We conclude that enhancement of the PRL-releasing effect of TRH by DA antagonism, a mechanism we previously observed in female rats during midlactation, proestrus, estrus, and metestrus using the present drug protocol, can be induced by estrogen and maintained by P. Further, our data suggest that the previously observed loss of this secretory mechanism on the morning of diestrus may be due to the decrease in plasma P that takes place between metestrus and diestrus.

Differential Regulation of the Nocturnal and Diurnal Prolactin Surges in Pregnant Rats Revealed by Dopamine Receptor Antagonism

“…Fagin and Neill [22] have shown that a transient fall in DA administered to hemipituitaries in vitro will enhance lactotroph sensitivity to TRH. This increased responsive ness to TRH following a brief decrease in DA has been demonstrated in vivo during several different endocrine states in female rats [23][24][25]. In vivo, pregnant rats re spond better to TRH during the nocturnal PRL surge compared to a nonsurge time [26,27], suggesting that a decrease in DA occurred previously.…”

Effects of Prolactin-Releasing Peptide on Tuberoinfundibular Dopaminergic Neuronal Activity and Prolactin Secretion in Estrogen-Treated Female Rats

“…A transformation of PRL from storage to a releasable pool in lactotrophs of the anterior pituitary has been proposed [7,26]. Similar changes in the release of hypothalamic DA and PRF may be the underlying mechanism preceding a PRL surge.…”

Prolactin Determinants in Healthy Women: A Large Cross-Sectional Study within the EPIC Cohort

“…Given the relatively large number of women with history of hormone therapy use and the association of prediagnostic prolactin levels with subsequent breast cancer risk more pronounced among women using hormone therapy (5), the current study has an importance also from a clinical perspective. However, further studies are needed to evaluate the effects of dose, exact formulation, specific mode of administration, and duration of hormone therapy on circulating prolactin levels (34)(35)(36).…”