PROLACTIN GENE-EXPRESSION AND SECRETION DURING PREGNANCY AND LACTATION IN THE RAT - ROLE OF DOPAMINE AND VASOACTIVE-INTESTINAL-PEPTIDE

It is known that dopamine (DA) is the major PRL-inhibiting factor, and vasoactive intestinal peptide (VIP) is one of the most potent and phy siological PRL-releasing factors. We have investigated the implication of DA and VIP in PRL gene expression and peptide secretion regulation during the physiological hyperprolactinemic states of pregnancy and l actation. Pregnant rats were studied on days 8, 15, and 20 of pregnanc y. Lactating rats suckled by eight pups were studied on days 3 and 8 o f postpartum, and nonsuckling postpartum rats were used as controls. P lasma estradiol, progesterone, and PRL were measured by RIA, as well a s pituitary immunoreactive (IR-) PRL, pituitary IR-VIP, and hypothalam ic IR-VIP. DA was studied by measuring changes in gene expression of t yrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine sy nthesis. TH, PRL, and VIP messenger RNA (mRNA) were assessed by Northe rn blot hybridization. The results showed very high plasma PRL levels in early pregnancy and during lactation, whereas plasma PRL concentrat ions were normalized at the end of gestation and in nonsuckling contro l rats. The physiological hyperprolactinemia of both early pregnancy a nd lactation correlated with higher pituitary PRL mRNA levels and lowe r pituitary IR-PRL content. Moreover, hypothalamic TH mRNA levels were lower in early pregnancy and lactation than at the end of gestation a nd in nonsuckling rats, respectively. The hypothalamic IR-VIP content was lower on day 8 of pregnancy than on days 15 and 20. However, VIP g ene expression in the hypothalamus did not change throughout pregnancy . During lactation, neither hypothalamic IR-VIP content nor VIP mRNA w as significantly altered. In the pituitary, IR-VIP content did not sig nificantly change, and VIP mRNA levels were higher on day 15 of pregna ncy than on the other days. During lactation, the pituitary IR-VIP con tent was very low on day 8 compared with those on day 3 of lactation a nd in nonsuckling control rats. VIP mRNA 1.0-kilobase transcript level s were higher in the lactating rats than in the control animals. These data show that both early pregnancy and lactation are physiological h yperprolactinemic states in which increased PRL mRNA accumulation coin cides with decreased IR-PRL content in the pituitary and higher plasma IR-PRL, indicating regulation at the gene expression level and of PRL secretion. Low TH gene expression also occurs during hyperprolactinem ia, suggesting that the diminution of DA activity that occurs during e arly pregnancy and lactation might be the major regulator of PRL alter ations. If hypothalamic VIP plays a role as a neuroendocrine PRL-relea sing factor during pregnancy and lactation, this may occur at the secr etory level, as suggested by the alterations in IR-VIP, with no modifi cations in VIP mRNA accumulation, in the hypothalamus. Pituitary VIP d oes not seem to be a major regulator of PRL secretion during pregnancy , whereas during lactation, it regulates PRL secretion in a paracrine and/or autocrine manner.