REGULATION OF GROWTH-HORMONE (GH) GENE-EXPRESSION AND SECRETION DURING PREGNANCY AND LACTATION IN THE RAT - ROLE OF INSULIN-LIKE GROWTH-FACTOR-I, SOMATOSTATIN, AND GH-RELEASING HORMONE

GH appears to play an important metabolic role during late pregnancy a nd in lactation maintenance. In this study, pregnant (days 8, 15, and 20 of gestation) and postpartum (days 3 and 8 postpartum, including la ctating and nonlactating dams) Wistar rats were used to investigate pi tuitary GH gene expression and hormone secretion, and the potential al terations of the major signals regulating GH secretion and action [som atostatin (SS) and GH-releasing hormone (GHRH), GH receptor (GH-R), an d insulin-like growth factor-I (IGF-I)]. GH and SS messenger RNA (mRNA ) were quantitated by Northern blot, and both IGF-I and GH-R mRNA were analyzed by the ribonuclease protection assay technique. Pituitary IR -GH content and GH mRNA increased at midpregnancy. IR-GH content was d ecreased in lactating rats. Plasma GH levels progressively increased d uring pregnancy, whereas no significant alterations were shown during lactation. Elevated GH levels persisted during lactation. Levels at th is time were higher in nonsuckling compared with suckling dams. Liver GH-R mRNA progressively decreased during pregnancy, but it remained un changed during lactation. Plasma IGF-I and liver IR-IGF-I constantly d ecreased during pregnancy, and no significant modifications were seen either in suckling or in nonsuckling animals. IGF-I mRNA accumulation in the liver decreased during pregnancy. After delivery, a progressive decrease of liver IGF-I mRNA occurred. At the hypothalamic level, a p rogressive increase in the IR-SS content was found during pregnancy, w ith no SS mRNA modification. After delivery, a higher hypothalamic IR- SS content was found in lactating than in nonlactating rats, with no c hanges in SS mRNA levels. Hypothalamic IR-IGF-I also showed a progress ive increase during pregnancy with no significant alterations during l actation. Hypothalamic IR-GHRH presented a nonsignificant mild increas e during pregnancy with no modifications during lactation. In the pitu itary, IR-IGF-I content progressively increased during gestation, reac hing its highest concentration at day 20. During lactation, pituitary IGF-I did not change. In summary, our data show that the mechanisms of the increase in plasma GH levels occurring during pregnancy include a n increase in GH gene expression in the pituitary, a decrease in SS se cretion from the hypothalamus, an increase in IR-IGF-I content in the hypothalamus and in the pituitary, and a significant decrease in circu lating IGF-I. Plasma and liver IR-IGF-I and IGF-I mRNA in the liver de creased throughout gestation due to a lower GH-R gene expression in th e liver. This state of GH resistance with a higher GH/IGF-I ratio coul d be important in providing supplementary nutrients to the fetus. Duri ng lactation, GH and its regulatory machinery did not show important m odifications.