Effect of Starvation and Subsequent Refeeding on Thyroid Function and Release of Hypothalamic Thyrotropin-Releasing Hormone

Abstract

Effects of starvation on thyroid function were studied in 5- to 6-week-old (R× U) F₁ rats. Starvation lowered plasma TSH in female, but not in male rats. Plasma T₄ and T₃ levels decreased, whereas the dialysable T₄ fraction increased during starvation. Free T₄ (FT₄) levels decreased rapidly in females, but only after prolonged fasting in male rats. Glucose decreased, and free fatty acid levels increased during starvation. Peripheral TRH levels did not change during food deprivation. Since effects of starvation were most apparent in young female rats, such rats were used to study hypothalamic TRH release during starvation and subsequent refeeding. Basal in vitro hypothalamic TRH secretion was less in starved rats than in control or refed animals. In vitro hypothalamic TRH release in medium with 56 ml KC1 increased 3-fold compared to basal release, and in these depolarization conditions TRH release was similar between hypothalami from control, starved and refed rats. In rats starved for 2 days, TRH level in hypophysial portal blood was lower than that of controls. Thus, diminished thyroid function during starvation may at least in part be caused by a reduced hypothalamic TRH release.

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].…”

Leptin Regulates Prothyrotropin-releasing Hormone Biosynthesis

“…Control experiments, including the incubation of cells without primary antibody or preimmune serum and the blocking of the primary antibody with synthetic peptides against which the antibody was generated, were performed and did not show any positive staining. For colocalization experiments, cells previously stained with anti-ObR antibody followed by fluorescein isothiocyanate probe (green color) were then incubated with anti-pAV 37 -Texas Red or anti-pST 10 -Texas Red antibody for 24 h at 4°C. Anti-pAV 37 antibody recognizes the TRH prohormone, and anti-pST 10 antibody recognizes the end product of processing prepro-TRH-(160 -169) (11).…”

“…For colocalization experiments, cells previously stained with anti-ObR antibody followed by fluorescein isothiocyanate probe (green color) were then incubated with anti-pAV 37 -Texas Red or anti-pST 10 -Texas Red antibody for 24 h at 4°C. Anti-pAV 37 antibody recognizes the TRH prohormone, and anti-pST 10 antibody recognizes the end product of processing prepro-TRH-(160 -169) (11). The conjugation of Texas Red (red color) to these antibodies, as well as their ability to obtain successful colocalization with other proteins, was described previously by us in experiments demonstrating the colocalization of pro-TRH with the prohormone convertase-1 (18).…”

“…After 12 days in culture, primary cultures of hypothalamic neurons were stimulated with leptin for 6 h in the presence of radioactive leucine (leucine is present 21 times in the pro-TRH sequence). After treatment, radioactive peptides were acid-extracted and subjected to double immunoprecipitation with an antibody, previously characterized by us (18), directed against prepro-TRH-(116 -151) (anti-pAV 37 antibody) that recognizes the TRH precursor (26 kDa) and an intermediate form of its processing of ϳ16 kDa. The immunoprecipitates were then subjected to separation on a Tricine/SDS-PAGE system, followed by slicing and radioactive counting.…”

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 .…”