Growth hormone (GH) is known to interact with adipose tissue and to induce lipolysis. Adipocytes produce leptin which regulates appetite and energy expenditure. In order to elucidate the role of GH in leptin production, we studied the effect of GH on leptin gene expression and body fat in fatty Zucker rats, a model of obesity with resistance to both leptin and insulin. Recombinant human GH administered subcutaneously at 0·5 mg/kg per day (low dose) as well as at 1·65 mg/kg per day (high dose) reduced leptin mRNA levels in epididymal fat tissue but not in subcutaneous fat tissue after 7 days. GH administration only at the high dose reduced percentage body fat. Insulin-like growth factor-I infusion (200 µg/kg per day) did not change percentage body fat or leptin mRNA levels in epididymal fat. These observations suggest that GH directly interacts with adipose tissue and reduces leptin gene expression in visceral fat tissue.

Abstract. In TSH-secreting pituitary adenomas (TSHoma), octreotide (OCT) therapy reduces tumor size and TSH secretion in some cases but not in others. As OCT acts through various types of somatostatin receptors (SSTRs), the different responses of TSHoma to OCT might be explained by the differences of SSTR expression. We therefore studied the expression of subtype-specific SSTR mRNA transcripts in tumor tissues by RT-PCR. Type 2 (SSTR2) mRNA transcripts were detected in all 8 tumors but those of SSTR3 and SSTR5 were demonstrated only in 5 of them. Serum TSH levels were decreased by OCT administration test in all patients but OCT therapy was effective in two patients out of three. SSTR5 mRNA was detected in two tumors from the responder, but not in one tumor that was resistant to OCT. These observations suggest that the temporal decrease of TSH by OCT may be mediated by SSTR2, and that the long term response to OCT therapy may be related with the expression of SSTR5. Therefore, the expression of SSTR5 in TSHoma may be a useful marker for predicting the outcome of the therapy, but further studies with larger numbers of patients are necessary.

Abstract. Leptin receptors are distributed throughout the body and leptin has been shown to have various effects. As we have recently demonstrated a positive correlation between serum leptin levels and TSH in euthyroid subjects, we investigated the effect of leptin on the thyroids. It was observed that serum leptin levels were negatively correlated with free thyroxine/TSH ratios in the serum of euthyroid female subjects. This suggests that leptin may modulate TSH effects. RT-PCR for leptin receptor expression revealed that FRTL-5 cells possess the gene transcript to the long cytoplasmic form of the receptor. Leptin actually appeared to induce an increase in c-fos mRNA expression. However, it inhibited iodide uptake typically induced by both TSH and dibutyryl cAMP, while leptin did not inhibit TSH-induced cAMP production or TSH-stimulated DNA synthesis in 4H medium (in the absence of insulin and TSH). Leptin also was observed to inhibit TSH-and dibutyryl cAMP-induced Na + /I -symporter and thyroglobulin mRNA expression. Lastly, leptin was seen to inhibit TSH-stimulated thymidine incorporation in 5H medium. Taken together, these results suggest that leptin suppresses TSH-induced thyroid function. Therefore, we hypothesized that leptin may be one of the regulators of thyroid function in obese patients. LEPTIN, the gene product of the ob gene, is produced by fat tissues and acts in an endocrine fashion by reporting the size of the adipose tissue mass to hypothalamic leptin receptors that ultimately control the appetite and energy expenditure [1]. Recent studies show that leptin receptors are widely distributed throughout the body and that they have a variety of effects on a number of tissues. For example, functional leptin receptors are expressed in the ovary where leptin mediates the signal between fat storage and the reproductive system [2]. As for the thyroid, we earlier demonstrated a positive relation between serum leptin and TSH levels in euthyroid subjects [3]. In addition to our data, Wesche et al. reported that in obese subjects a larger thyroid size was associated with slightly but significantly higher TSH and lower free thyroxine (fT 4 ) serum levels [4]. As serum leptin concentrations positively correlate with body fat mass or body mass index, serum leptin levels should be higher in the obese subjects. We therefore assumed that leptin stimulates proliferation of thyroid cells or inhibits thyroid hormone synthesis stimulated by TSH in obese subjects by some mechanism. In order to clarify the possible role of leptin in regulation of thyroid function, we first analyzed the relation between serum leptin concentrations and fT 4 /TSH ratio in order to re-confirm the clinical relationship between obesity and thyroid function in euthyroid subjects. Next we investigated the direct actions of leptin on

Although endothelins were originally discovered as peptides with vasoconstrictor activity, recent studies have indicated a number of endothelin (ET)-induced hormonal functions in various tissues. We have studied the interaction of endothelins with porcine thyroid cells in culture. Specific binding of 125I-labelled ET-1 was demonstrated in porcine thyroid cells. The binding was displaced equally by unlabelled ET-1 and ET-2, but receptor affinity for ET-3 was lower than that for ET-1 and -2. Scatchard analysis of the data revealed a single class of high-affinity ET-1 receptors with a Kd of 0.45 nmol/l and a binding capacity of 2100 sites/cell. SDS-PAGE and autoradiography of 125I-labelled ET-1 cross-linked with thyroid cell membranes demonstrated ET-1 binding sites with an apparent molecular weight of 50 kDa. These results indicated that ET-1 receptors in thyroid cells are type A ET receptors. In association with the presence of ET-1 receptors, porcine thyroid cells responded to ET-1 and ET-2 with an increase in c-fos mRNA expression. Although ET-1 did not affect DNA synthesis stimulated by either EGF or IGF-I, it dose-dependently inhibited TSH-induced iodide uptake and also inhibited iodide uptake stimulated by forskolin and 8-bromo-cAMP. ET-1 had no effect on TSH-stimulated cAMP production. Thus, ET-1 inhibited TSH-induced iodine metabolism by acting at the steps distal to cAMP production. In agreement with a recent report, immunoreactive ET-1 was detected in medium conditioned by porcine thyroid cells. Antibody to ET-1 was found to increase TSH-induced iodide uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

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