Starvation-induced changes in the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA and the hypothalamic release of proTRH-derived peptides: role of the adrenal gland

Abstract

The purpose of this study was to investigate the mechanisms involved in the reduced thyroid function in starved, young female rats. Food deprivation for 3 days reduced the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA, the amount of proTRH-derived peptides (TRH and proTRH160-169) in the paraventricular nucleus, the release of proTRH-derived peptides into hypophysial portal blood and the pituitary levels of TSH beta mRNA. Plasma TSH was either not affected or slightly reduced by starvation, but food deprivation induced marked increases in plasma corticosterone and decreases in plasma thyroid hormones. Refeeding after starvation normalized these parameters. Since the molar ratio of TRH and proTRH160-169 in hypophysial portal blood was not affected by food deprivation, it seems unlikely that proTRH processing is altered by starvation. The median eminence content of pGlu-His-Pro-Gly (TRH-Gly, a presumed immediate precursor of TRH), proTRH160-169 or TRH were not affected by food deprivation. Since median eminence TRH-Gly levels were very low compared with other proTRH-derived peptides it is unlikely that alpha-amidation is a rate-limiting step in hypothalamic TRH synthesis. Possible negative effects of the increased corticosterone levels during starvation on proTRH and TSH synthesis were studied in adrenalectomized rats which were treated with corticosterone in their drinking water (0.2 mg/ml). In this way, the starvation-induced increase in plasma corticosterone could be prevented. Although plasma levels of thyroid hormones remained reduced, food deprivation no longer had negative effects on hypothalamic proTRH mRNA, pituitary TSH beta mRNA and plasma TSH in starved adrenalectomized rats. Thus, high levels of corticosteroids seem to exert negative effects on the synthesis and release of proTRH and TSH. This conclusion is corroborated by the observation that TRH release into hypophysial portal blood became reduced after administration of the synthetic glucocorticosteroid dexamethasone. On the basis of these results, it is suggested that the reduced thyroid function during starvation is due to a reduced synthesis and release of TRH and TSH. Furthermore, the reduced TRH and TSH synthesis during food deprivation are probably caused by the starvation-induced enhanced adrenal secretion of corticosterone.

Polymorphisms in the serotonin reuptake transporter gene modify the consequences of social status on metabolic health in female rhesus monkeys

“…Within s-variant females, dominant females had higher levels than subordinate animals. Thyroid hormones are reduced by hypercortisolism associated with chronic disease [75] as well as restraint stress [76] and food restriction [77,78], effects that may be mediated through a reduction in hypothalamic TRH expression. However, other data indicate this decrease induced by food restriction [47] and stress [48] may occur independent of changes in TRH expression.…”

Interactions between the melanocortin system and the hypothalamo–pituitary–thyroid axis

“…It has been well characterised that in states of negative energy balance, such as prolonged fasting, regulation of the HPT axis is altered, as manifested by low plasma T3, and T4, with a low or inappropriately normal TSH and a reduction in TRH biosynthesis and secretion [1,5,9,15,16,25,27,33,51,64]. This central hypothyroidism following starvation may be an important adaptive response, by reducing thermogenesis and hence, reducing the obligatory use of energy stores [21].…”

α-Melanocyte-Stimulating Hormone Is Contained in Nerve Terminals Innervating Thyrotropin-Releasing Hormone-Synthesizing Neurons in the Hypothalamic Paraventricular Nucleus and Prevents Fasting-Induced Suppression of Prothyrotropin-Releasing Hormone Gene Expression

“…During fasting, however, when thyroid hormone levels fall, a seemingly paradoxical reduction in hypophysiotropic TRH and an inappropriately normal or low plasma thyrotropin (TSH) are observed, consistent with central hypothyroidism (Rondeel et al, 1992;van Haasteren et al, 1995;Legradi et al, 1997). These alterations can be completely reversed by the systemic administration of leptin to fasting animals (Legradi et al, 1997), leading us to propose that the arcuate nucleus, a major locus for the central actions of leptin (Hakansson et al, 1996;Huang et al, 1996;Mercer et al, 1996;Schwartz et al, 1996), can reset the sensitivity of hypophysiotropic neurons to the feedback effects of thyroid hormone .…”