We have investigated the effects of increasing gestational age, maternal undernutrition or restricted placental growth on prolactin receptor (PRLR) gene expression in perirenal adipose tissue collected from foetal sheep during late gestation (term = 147 d +/- 3 d of gestation). Foetal nutrient supply was reduced by either restriction of placental growth following removal of endometrial caruncles before mating or by reducing maternal feed intake by 50% from 115 d of gestation. Total RNA was extracted from adipose tissue taken from foetal sheep between 90 and 145 d of gestation, and only at 141-145 d in placentally restricted, nutrient restricted and control foetuses. Messenger RNAs encoding the long (PRLR1) and short (PRLR2) forms of the PRLR and glyceraldehyde-phosphate-dehydrogenase (GAPDH) were detected and quantified in a ribonuclease protection assay using an antisense RNA probe complementary to ovine PRLR2 and GAPDH. There was a 7.5-fold increase in the amount of perirenal adipose tissue between 90 and 125 d of gestation, compared with a 1.3-fold increase between 125 and 145 d of gestation. The abundance of mRNA encoding PRLR1 and PRLR2 in perirenal adipose tissue increased 10- and sixfold, respectively, between 90 and 125 d of gestation, and then declined by 145 d of gestation. Both placental restriction and maternal undernutrition significantly reduced foetal adipose tissue deposition. The abundance of PRLR1 but not PRLR2 mRNA was reduced in adipose tissue from the placentally restricted group, where as GAPDH mRNA was three times higher than in controls. In contrast, maternal undernutrition from 115 d of gestation did not affect PRLR1, PRLR2 or GAPDH mRNA expression in foetal adipose tissue. It is concluded that during the period of rapid deposition of perirenal adipose tissue, there is a concomitant increase in PRLR gene expression. This indicates that prolactin may play an important role in the growth and maturation of foetal adipose tissue which occurs before birth.

Goitre was induced in adult rats by acute (1 or 2 weeks) or chronic (4 or 10 weeks) administration of methimazole together with a low iodine diet. Involution of thyroid growth was then observed at 16 weeks, 4 weeks after withdrawal of goitrogens and reversion to a normal diet. Experimental animals quickly became hypothyroid compared with controls and exhibited thyroid hyperplasia (control (n = 10): total serum thyroxine (T4) 66 +/- 4 nmol/l, thyroid weight 5 +/- 1 mg/100 g body weight, means +/- S.D.; experimental (n = 10): T4 undetectable, thyroid weight 27 +/- 4 mg/100 g body weight after 2 weeks of treatment). Thyroid growth rate subsequently slowed between 2 and 10 weeks. Messenger RNA for basic fibroblast growth factor (basic FGF) and for the high-affinity FGF receptor, was compared in the thyroids and livers of control and goitrous rats by ribonuclease protection assay. Low levels of mRNA for basic FGF and its receptor were detectable in thyroids from control rats at all times, while none was detected in the livers from any animal. Basic FGF and receptor mRNAs increased, and were detected at greatest abundance in hyperplastic thyroids at 1 and 2 weeks respectively, during goitre formation, but subsequently declined in parallel with thyroid growth rate at 4 and 10 weeks. When quantified by radioimmunoassay, basic FGF extracted from thyroids was fivefold greater than in controls after 1 week of goitrogen treatment (control (n = 4): 24 +/- 9 pmol/micrograms DNA; goitre (n = 4): 100 +/- 16 pmol/micrograms DNA; P < 0.05). Basic FGF and FGF receptor mRNAs localized by in situ hybridization predominantly to the epithelial cell population within follicles. Localization by immunohistochemistry demonstrated that basic FGF was present in the thyroids of control rats, and was largely associated with the basement membrane of follicles. During thyroid hyperplasia, increased basic FGF immunoreactivity appeared over the cytoplasm of follicular epithelial cells and was lost from the extracellular matrix. Thyroid involution following removal of goitrogen/low iodine treatment was associated with a decrease in mRNA for basic FGF or its receptor, and a loss of immunoreactive basic FGF from the cytoplasm of follicular cells. These results suggest that autocrine expression of basic FGF and FGF receptor could contribute to thyroid hyperplasia in rats.

We have investigated the effects of restriction of placental growth on foetal adrenal growth and adrenal expression of mRNAs for Insulin-like Growth Factor II (IGF-II), the IGF binding protein IGFBP-2, Steroidogenic Factor 1 (SF-1) and adrenocorticotrophic hormone (ACTH) receptor (ACTH-R) and the steroidogenic cytochrome P-450 enzymes: cholesterol side chain cleavage (CYP11A1), 17alpha-hydroxylase (CYP17) and 21-hydroxylase (CYP21A1); and 3beta-hydroxysteroid dehydrogenase/Delta5Delta4 isomerase (3betaHSD). Endometrial caruncles were removed from non-pregnant ewes before mating (placental restriction group; PR). The total adrenal: foetal weight ratio was higher in PR (n=6 foetuses) than in control foetuses (n=6 foetuses). There was no difference in plasma ACTH concentrations between the PR and control foetuses between 130 and 140 days gestation. Adrenal IGF-II mRNA levels were lower (P<0.05) in the PR group, however, adrenal IGFBP-2 mRNA levels were not different between the PR and control groups. Adrenal ACTH-R mRNA levels were also lower whilst CYP11A1 mRNA levels were increased (P<0.005) in the PR group. We conclude that foetal adrenal growth and steroidogenesis are stimulated as a consequence of foetal growth restriction and that factors other than ACTH are important in foetal adrenal activation during chronic, sustained hypoxaemia.