Abstract. Thyrotoxicosis is associated with increased skeletal muscle glucose metabolism and lipid oxidation in the fasted state. Conversely, in hypothyroidism, glucose metabolism is reduced. The present study has assessed in patients the effects of chronic thyroid hormone deficiency, on insulin-stimulated skeletal muscle metabolism, using a combination of the forearm and hyperinsulinaemic euglycaemic clamp techniques. Seven female patients presenting with primary auto-immune hypothyroidism were studied at presentation and 4-9 months after being rendered biochemically euthyroid. No significant differences were demonstrated between the hypothroid and euthyroid states in forearm muscle blood flow, or in glucose or lipid metabolism.

Activin A is a homodimer of inhibin beta A subunits, and was first isolated from gonadal fluids on the basis of its ability to stimulate FSH secretion by rat pituitary cells in vitro. The beta A subunits of activin and their mRNAs have been found in many cell types, in several species and at different stages of development, suggesting that activin A has a wide range of diverse biological roles. Apart from the modulation of gonadotroph function, in-vitro studies have demonstrated inhibitory effects of activin A on GH synthesis, GH secretion and possibly somatotroph proliferation. We have therefore investigated the potential role of activin A in the pathophysiological regulation of GH secretion by human somatotrophinoma cells using in-vitro techniques. Cell cultures were established by enzyme dispersion of adenoma tissue obtained from six patients with acromegaly, and treated for 72 h with 0.01-10 nmol recombinant human activin A/l followed by a 2-h stimulation test with 10 nmol GH-releasing factor (GRF)/l. Medium was collected at 24, 48 and 72 h, as well as after GRF treatment, and GH concentrations were measured by immunoradiometric assay. Basal GH secretion from the cells of two tumours was significantly stimulated 12-63% above control values during treatment with 0.01-10 nmol activin A/l, whereas the peptide had no effect on GH release from cells of the remainder of the tumours. GRF significantly stimulated GH release from the cells of two different adenomas, and pretreatment with 0.01-1 nmol activin A/1 partially but significantly blocked GRF-stimulated GH release from the cells of one of these.(ABSTRACT TRUNCATED AT 250 WORDS)

SUMMARY Assays for human growth hormone (HGH) were carried out on 89 acromegalic patients, 81 of whom were studied before any treatment had been given. Serial studies were undertaken, generally at 6-monthly intervals, with the same test procedure, using a 50 g oral glucose tolerance test (GTT) and identical assay conditions over a period of 8 years. Twenty-three patients were assessed at intervals during periods of up to 4 years whilst they remained untreated. The general picture was one of unchanging HGH levels. Ten patients were studied before and after external irradiation. HGH levels showed a slow continuing fall for as long as 4 years and thereafter they stabilized at one-third of pretreatment values. HGH levels in 12 patients treated with radioactive implants showed an immediate fall to one-third, and thereafter a further slow decline to one-tenth of pretreatment levels. The response in eight patients treated by surgical removal of pituitary tissue and subsequent radiotherapy varied considerably. No patient, treated or untreated, showed evidence of partial suppression of HGH secretion during the GTT although three patients consistently responded to glucose with paradoxical hypersecretion.

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Insulin-like growth factor-I (IGF-I) and IGF-II receptors have previously been demonstrated on membranes prepared from human somatotrophinomas. IGF-I has been shown to have a variable effect on GH secretion by these tumours in vitro. The effects of purified IGF-II on GH secretion have not been described. We have studied the direct actions of human recombinant IGF-II on GH release from eight somatotrophinomas cultured in vitro. Somatotrophinoma cells were cultured as monolayers at a density of 10(5) cells/0.5 ml. Treatment with IGF-II for 4 and 24 h resulted in discrete inhibitory effects on GH release from two tumours (tumour 5: 4 h, IGF-II 0.5 nmol/l; tumour 2; 24 h, IGF-II 1 nmol/l). Treatment with IGF-II for 24 h resulted in significant inhibitory effects on GH release from one tumour over a range of concentrations tested (IGF-II 0.5-10 nmol/l). Addition of human GH-releasing factor (hGRF) (1-44) (20 nmol/l) for 4 and 24 h resulted in stimulation of GH release by five tumours. Two tumours demonstrated significant inhibitory effects of IGF-II on GRF-stimulated GH release (tumour 2: 24 h, IGF-II 1-5 nmol/l; tumour 3; 4 h, IGF-II 5 nmol/l; 24 h, IGF-II 0.5-50 nmol/l). These data emphasize the heterogeneity of somatotrophinomas in terms of their response to modulators of GH secretion. IGF-II does not appear to have a modulatory role on GH release by most somatotrophinomas.