It was possible to vary the replication rate of cells in the islets of Langerhans of adult rats. The rate of incorporation of [3H]thymidine into islet DNA was increased at 12 days of pregnancy to 2.3-fold and at 19 days of pregnancy to 1.3-fold that in control rats. Ovariectomy, which leads to lowered plasma levels of ovarian steroids, induced a significant and unexpected increase in the rate of thymidine incorporation into islets; treatment of ovariectomized rats with 2 micrograms oestradiol/rat per day for 3 days reversed this upward trend. When islets from normal rats were cultured with certain combinations of steroid hormones including progesterone and oestradiol or with insulin secretagogues, with the exception of glucose, a decreased rate of DNA synthesis was usually found compared with that in control rats. Since treatment with steroid hormones inhibited incorporation of [3H]thymidine into islets from ovariectomized rats and directly reduced incorporation into tissue-cultured islets from normal rats in vitro, it was concluded that increased levels of steroid hormones were not responsible for the higher rate of regeneration of islet cells in pregnant rats. However, a striking correlation between levels of blood glucose in vivo and DNA synthesis in islets in vitro has been observed.

Ovariectomized rats showed a 30% increase in body weight and food intake over a 9 day period after operation. When pair-fed with normal controls, they had comparatively higher fasting serum levels of glucose and lower levels of insulin and progesterone than the normal rats. Treatment with oestradiol reversed these results. Insulin release from islets isolated from ovariectomized rats was significantly lower than from those of normal controls; the secretory responses were improved after administration of oestradiol to ovariectomized rats. Cytosol receptors for progesterone and oestradiol were measured in a 105 000 g supernatant fraction of islets from normal, ovariectomized and oestrogen-treated ovariectomized rats. Progesterone-receptor binding was dramatically reduced after ovariectomy but was restored to normal levels by oestradiol treatment of the rats. Oestradiol-receptor binding was not significantly affected by ovariectomy but was increased several fold by oestrogen treatment of ovariectomized rats. These results suggest that islets of Langerhans contain receptors for both progesterone and oestradiol, and that this receptor population is subject to change. Progesterone--but not oestradiol--receptor measurements could be correlated with alterations in the rates of secretion of insulin from islets. Oestrogen administration in vivo had profound effects on subsequent insulin release from islets, though this may have been mediated by way of an increase in the quantity of the progesterone receptor.

Available experimental data suggest that adiponectin and thyroid hormones have biological interaction in vivo. However, the effects of thyroid hormones on adipose adiponectin gene expression in thyroid dysfunction are unclear. We induced hyper- (HYPER) and hypothyroidism (HYPO) by daily administration of a 12 mg/l of levothyroxine and 250 mg/l of methimazole in drinking water of rats, respectively, for 42 days. The white adipose tissues and serum sample were taken on days 15, 28, 42 and also 2 weeks after treatment cessation. Analysis of adiponectin gene expression was performed by real-time PCR and 2(-ΔΔct) method. The levels of adipose tissue adiponectin mRNA in the HYPO rats were decreased during the 6-week treatment when compared to control rats (<0.05) and were increased significantly 2 weeks after HYPO cessation (P < 0.05). This decline in adiponectin gene expression occurred in parallel with a decrease in T3, T4, fT3 and fT4 concentrations (P < 0.05). In opposite to HYPO rats, adipose adiponectin gene expression was increased in HYPER rats during the 6-week treatment in parallel with an increase the thyroid hormones concentrations (P < 0.05), and its expression was decreased 2 weeks after HYPER cessation (P < 0.05). Adiponectin gene expression levels showed significant negative correlations with concentrations of LDL (HYPO; r = -0.806, P = 0.001 and HYPER; r = -0.749, P = 0.002), triglyceride (HYPO; r = -0.825, P = 0.001 and HYPER; r = -0.824, P = 0.001) and significant positive correlations with concentrations of glucose (HYPO; r = 0.674, P = 0.004 and HYPER; r = 0.866, P = 0.001) and HDL (HYPO; r = 0.755, P = 0.001 and HYPER; r = 0.839, P = 0.001). The current study provides evidence that adiponectin gene expression in adipose tissue is regulated by thyroid hormones at the translation level and that lipid and carbohydrate disturbances in a patient with thyroid dysfunction may be, in part, due to adiponectin gene expression changes.

Summary.Islets of Langerhans isolated from normal female rats have been used in studies of 3H-progesterone uptake by intact islet cells. The intracellular sites which are involved in binding of the hormones have been determined by subcellular fractionation and autoradiography. Uptake of 3H-progesterone into islets occurred in a temperature and concentration dependent manner. The uptake increased rapidly in the first 30 min, and could be partially displaced by addition of excess unlabelled progesterone. 3H-progesterone uptake was lowered by incubation of the islets in the absence of Ca ++, at 0 ° compared to 37 ° C, or to a much lesser extent when islet cycilic AMP levels were raised by addition of 3-isobutyl-1-methylxanthine. However, uptake was unaffected by prior treatment of the islets with neuraminidase or phydroxymercuribenzoate. Differential centrifugation of islets which had previously been incubated with 3H-progesterone showed the highest specific activity of binding in the nuclei and debris fraction. Isolation of a purified nuclear fraction by sedimentation through sucrose solutions confirmed that binding was present in the nuclear component of this heterogeneous fraction, while autoradiographic studies suggested both nuclear and cytosolic localisation of 3H-progesterone. In a separate series of experiments, evidence was obtained for the existence of saturable cytosolic binding of progesterone, and for movement of labelled hormone from the cytosol to the nuclear fraction.It is suggested that, in the islets of Langerhans as in other target tissues, the action of progesterone involves penetration into the cells, binding to a cytosolic receptor protein, and subsequent transfer to the nucleus. The nuclear events which lead to subse-

The aim of this study was to examine whether the relative gene expression of AdipoR1 and AdipoR2 in rat adipose tissue is altered by thyroid hormones, and whether this might relate to their circulating thyroid hormones and adiponectin levels. Hyper- and hypothyroidism were induced by daily oral administration of levothyroxine and methimazole in rats, respectively, over a 42 days period. Real-time PCR analysis was performed to evaluate the changes in AdipoR1 and AdipoR2 mRNA levels in the adipose tissue on days 15, 28, 42, and also 2 weeks after the cessation of treatment. In response to treatment with methimazole, mRNA levels of AdipoR1 and AdipoR2 decreased in the white adipose tissue compared to the euthyroid rats (p < 0.05). This decline was reversible 2 weeks after treatment cessation. The mRNA levels of AdipoR1 and AdipoR2 were increased in the hyperthyroid group of animals compared to euthyroid control (p < 0.05), and its changes were reversible 2 weeks after treatment cessation (P < 0.05). Adiponectin receptors gene expression levels in the adipose tissue of treated animals have positive correlations with thyroid hormones concentrations. Our results suggest that AdipoR1 and AdipoR2 gene expression is regulated by thyroid hormones in hypo- and hyperthyroidism.