Presence of extrathyroidal TSH-receptor, with special reference to its role in neonatal regulation of lipolysis

Abstract: At birth, the newborn child must utilize stored energy until lactation is established. The main source of energy is fat - that is, triglycerides stored in the white adipose tissue. This study deals with hormonal regulation of lipolysis in the neonatal period. In experiments on isolated adipocytes obtained from infants during surgery for inguinal hernia, thyroid-stimulating hormone (thyrotropin, TSH) has been shown to have a lipolytic effect. Newborn infants have peak values 50-100 times higher than normal adult values in the first hour after birth and our hypothesis is that the TSH peak helps the infant to mobilize stored energy at the right time. In this study, we show that human recombinant TSH is as effective as the previously used pituitary bovine preparation in stimulating lipolysis. We also show that the TSH-receptor (TSHR), which mediates TSH actions in the thyroid gland, is also expressed in isolated adipocytes from infants and adults, using Northern blot analysis and RT-PCR (Paper I). The effects of TSH on adipocytes can be mimicked or inhibited by antibodies directed at the TSHR, and stimulation by TSH seems to activate the second messenger cyclic AMP (Paper Il). We found no effect of growth hormone on TSH-induced or isoprenaline-induced lipolysis, and no acute lipolytic effect of GH on infant adipocytes (Paper III). When comparing effects of the antilipolytic hormone insulin on TSH- and isoprenaline induced lipolysis, we demonstrate an inhibitory effect (as expected) of insulin on isoprenaline induced lipolysis, whereas lipolysis induced by TSH is not affected by addition of insulin. This may explain the unimpaired lipolysis observed in infants of diabetic mothers (Paper IV). We demonstrate the expression of functional TSHR in the human heart, which can serve as an antigen for antibodies seen in Graves' disease (Paper V). Thyroid-associated ophthalmopathy (TAO) is common in patients with Graves' disease. TAO is considered an autoimmune disease and TSHR has been found in retroorbital tissue. This is the first study to show TSHR in isolated human retroorbital adipocytes and experiments with lipolysis suggest the expression of a functional TSHR in these adipocytes (Paper VI). Key words: adaptation, adipocytes, Graves' disease, growth hormone, human, hyper thyroidism, infant, insulin, metabolism, TSHR stimulating antibodies, thyrotropin, TSH. ISBN: 91-628-2886-X