ROLE OF THE HYPOTHALAMUS IN PITUITARY-THYROID INTERPLAY

Abstract

SUMMARY Experimental analysis of the rat's hypothalamic-hypophysial-thyroid system, utilizing stereotaxic, radiometric, histochemical, and bioassay procedures, indicated that electrolytic lesions in the anterior and tuberal portions of the hypothalamus altered thyrotrophic hormone (TSH) secretion in the adenohypophysis and reduced thyroid function (histology and 131I release from the gland). Inhibition of thyroidal radio-iodine release was found within 2 weeks after hypothalamic destruction and was greater in rats which became obese. Significant reduction in titres of circulating TSH also occurred. TSH concentration in the smaller pituitaries of animals in which lesions had been made remained normal, but total hormonal stores decreased. Thyroxine and triiodothyronine suppressed markedly and equally TSH secretion in the adenohypophyses of operated and intact rats; triiodothyronine was more potent (about 5:1). Hypothalamic damage did not prevent the re-accumulation of TSH in pituitaries previously depleted of their hormone by propylthiouracil; pituitary TSH concentrations rebounded to supranormal levels, but titres in blood decreased to subnormal values. The physiological and histochemical changes induced in the adenohypophyses of rats with lesions strongly implicated the basophils (β cells) in the genesis of TSH. All anterior pituitary cell types were affected in hypothalamic deficiency, but only the β basophils persisted when TSH stores were high, or disappeared when the pituitary was depleted of TSH with exogenous thyroid hormone. The experimental results indicated that the hypothalamus modulates the activity of the pituitary-thyroid system by influencing production and release of TSH by the pituitary. Hypothalamic regulation of TSH secretion exists for normal conditions as well as for those situations in which enhanced TSH secretion is required. The maintenance of abundant TSH reserves in the adenohypophysis, their depletion after thyroid hormone, and their re-accumulation after goitrogen withdrawal, nevertheless revealed: (1) that the 'isolated' rat pituitary possesses a good measure of autonomous TSH function; (2) that thyroid hormone can act directly on the adenohypophysis independently of the hypothalamus; and (3) that the basic thyroid-pituitary servomechanism is systemically controlled by circulatory levels of thyroid hormone and is not under neural domination.