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 physiological 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 lactation. Pregnant rats were studied on days 8, 15, and 20 of pregnancy. Lactating rats suckled by eight pups were studied on days 3 and 8 of postpartum, and nonsuckling postpartum rats were used as controls. Plasma estradiol, progesterone, and PRL were measured by RIA, as well as pituitary immunoreactive (IR-) PRL, pituitary IR-VIP, and hypothalamic IR-VIP. DA was studied by measuring changes in gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. TH, PRL, and VIP messenger RNA (mRNA) were assessed by Northern blot hybridization. The results showed very high plasma PRL levels in early pregnancy and during lactation, whereas plasma PRL concentrations were normalized at the end of gestation and in nonsuckling control rats. The physiological hyperprolactinemia of both early pregnancy and lactation correlated with higher pituitary PRL mRNA levels and lower pituitary IR-PRL content. Moreover, hypothalamic TH mRNA levels were lower in early pregnancy and lactation than at the end of gestation and in nonsuckling rats, respectively. The hypothalamic IR-VIP content was lower on day 8 of pregnancy than on days 15 and 20. However, VIP gene expression in the hypothalamus did not change throughout pregnancy. During lactation, neither hypothalamic IR-VIP content nor VIP mRNA was significantly altered. In the pituitary, IR-VIP content did not significantly change, and VIP mRNA levels were higher on day 15 of pregnancy than on the other days. During lactation, the pituitary IR-VIP content was very low on day 8 compared with those on day 3 of lactation and in nonsuckling control rats. VIP mRNA 1.0-kilobase transcript levels were higher in the lactating rats than in the control animals. These data show that both early pregnancy and lactation are physiological hyperprolactinemic states in which increased PRL mRNA accumulation coincides 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 hyperprolactinemia, suggesting that the diminution of DA activity that occurs during early pregnancy and lactation might be the major regulator of PRL alterations. If hypothalamic VIP plays a role as a neuroendocrine PRL-releasing factor during pregnancy and lactation, this may occur at the secretory level, as suggested by the alterations in IR-VIP, with no modifications in VIP mRNA accumulation, in the hypothalamus. Pituitary VIP does 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.
Escalada
J
J
Endocrinology Services, Centro Nacional de Investigación Clínica, Instituto Carlos III, Madrid, Spain.
Cacicedo
L
L
Ortego
J
J
Melian
E
E
Sánchez-Franco
F
F
D000818:Animals; D000833:Animals, Suckling / Q000097:blood; D004298:Dopamine / Q000502:physiology*; D004958:Estradiol / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000378:metabolism; D007774:Lactation / Q000502:physiology*; D010902:Pituitary Gland / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000502:physiology*; D011374:Progesterone / Q000097:blood; D011388:Prolactin / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide; D011374:Progesterone; D004958:Estradiol; D011388:Prolactin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine