Pituitary Changes Involved in Prolactin Secretion Induced by Mifepristone and Naloxone during Late Pregnancy

Abstract

Background/Aims: The antiprogesterone mifepristone facilitates prolactin release, an effect enhanced by administration of the opioid antagonist naloxone. The present study explores ultrastructural changes in lactotropes after mifepristone and naloxone administration, correlating them with the expression of pituitary prolactin. Methods/Results: Rats were sacrificed at 18:00 h on day 19 of pregnancy. Prolactin immunoelectron microscopy of lactotropes from control rats showed characteristics of quiescent cells with numerous small and spherical secretory granules. Naloxone administration did not modify lactotrope morphology or prolactin expression in terms of mRNA or protein abundances. Mifepristone treatment induced lactotrope activation with development of the rough endoplasmic reticulum and Golgi complex with prolactin immunoreactive small newly formed and large mature secretory granules. Mifepristone increased prolactin mRNA and protein expression. Naloxone administration to mifepristone-treated rats potentiated lactotrope activation compared with mifepristone alone showing exocytotic images of prolactin granules and some cells with evident signs of involution. Conclusions: (1) Blockade of progesterone action by mifepristone activated the lactotrope, increased significantly prolactin mRNA and protein expression and prepared the pituitary for naloxone action. (2) The high serum prolactin levels induced by mifepristone and naloxone may regulate negatively lactotrope activity as suggested by the presence of regressing cells neighboring the actively secreting cells.

Effect of Progesterone Withdrawal on Hypothalamic Mechanisms Related to Prolactin Release in Late Pregnant Rats

“…The increased PRLR long mRNA content, if paralleled by an increase in the receptor protein, may also be a stimulus for induction of TH by the elevated PRL, counteracting the effect of P 4 decline. Although it has been shown that TIDA neuron responsiveness to PRL, measured as STAT5 activation [10], is decreased at the end of pregnancy and during lactation, accompanied with decreased TH expression [32,34], comparison of our results with those of Gabutti et al [47] may indicate that some degree of sensitivity to PRL is maintained. However, we found increased expression of SOCS family members mRNA after P 4 fall, confirming the results obtained by Steyn et al [9] using a different experimental model of P 4 withdrawal.…”

Female Pituitary Size in Relation to Age and Hormonal Factors

“…A return to normal size between the first week and 6 months postpartum has been described [4,5]. Furthermore, an alteration of pituitary function by some drugs, which are frequently applied in late pregnancy, was found [13]. In postmenopausal women, cranio-caudal diameters were found to be significantly larger in individuals with estrogen substitution, compared to no substitution [7].…”

Opioid modulation of prolactin secretion induced by stress during late pregnancy. Role of ovarian steroids

“…2b). Two-way ANOVA analysis was as follows: Drug factor (SAL, NAL) F Experiment 2: effect of progesterone, estrogen and NAL on prolactin secretion in stressed rats We previously showed that 5 mg/kg [11,14] or 10 mg/kg [7,8] Mp treatment 10 or 12 h before NAL administration induced prolactin secretion, while 2 mg/kg treatment did not. The present study used a 2 mg/kg Mp dose so no changes in prolactin secretion after SAL or NAL administration were expected.…”

“…Moreover, Mp inhibits the hypothalamic dopaminergic neuronal system [11], the main inhibitory factor of prolactin secretion in terms of dopaminergic transmission and tyrosine hydroxylase (TH) expression [12,13]. This effect enables a significant activation of lactotrophs and primes the pituitary for a subsequent stimulatory action of NAL [14].…”