Effects of long-term food reduction on the hypothalamus-pituitary-thyroid axis in male and female rats

Abstract

The reduced thyroid activity during short-term starvation is associated with a lowered hypothalamic synthesis and secretion of TRH. However, little is known about the cause of the reduced thyroid function during prolonged malnutrition. We have therefore studied the effects of food reduction to one-third of normal (FR33) on the hypothalamus-pituitary-thyroid axis of male and female Wistar rats. After 3 weeks body weights of FR33 rats were almost 50% lower than those of controls. In both sexes, FR33 caused marked increases in serum corticosterone, and decreases in serum TSH, thyroxine (T4), free T4, tri-iodothyronine (T3) and free T3. While the free T3 fraction (FFT3) in serum decreased, the free T4 fraction (FFT4) tended to increase. Electrophoretic analysis indicated that decreased FFT3 was correlated with an increased thyroxine-binding globulin, while the increase in FFT4 seemed due to a decreased thyroxine-binding prealbumin binding capacity. Total RNA and proTRH mRNA in the hypothalamus were not affected by FR33. Median eminence and posterior pituitary TRH content tended to increase in FR33 rats, suggesting that hypothalamic TRH release is reduced in FR33 rats. Anterior pituitary TSH content was decreased by FR33 in both sexes, but pituitary TSH beta mRNA and TRH receptor status were not affected except for increased pituitary TSH beta mRNA in female FR33 rats. Although FR33 had no effect on pituitary weight, pituitary RNA and membrane protein content in FR33 rats were 50-70% lower than values in controls. In conclusion, prolonged food reduction suppresses the pituitary-thyroid axis in rats. In contrast to short-term food deprivation, the mechanism whereby serum TSH is suppressed does not appear to involve decreases in proTRH gene expression, but may include effects on pituitary mRNA translation. Our results further support the hypothesis that TSH release may be lowered by increased corticosterone secretion, although the mechanism of this effect may differ between acute starvation and prolonged food reduction.

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

“…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. Because we did not observe differences in T4, the decrease in T3 may be due to a disruption in type 2 deiodinase activity (D2).…”

“…Insulin and glucose were measured as indices of energy homeostasis [46]. Finally, the thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were measured, as these hormones are decreased by reduced food intake [47] and exposure to chronic stressors [48].…”

Longitudinal evidence of the impact of normal thyroid stimulating hormone variations on cognitive functioning in very old age

“…The results suggest that although most of the association between TSH and cognitive abilities may be due to shared change variation, TSH may exert a direct impact on episodic memory. It is suggested that the mechanism for such effects are increased cortisol levels, known to affect episodic memory functioning in particular (Lupien et al, 1994;van Haasteren et al, 1996). In order to further clarify this topic, it is necessary to expand the age range under scrutiny to cover both younger and older participants, and to add indicators of both relevant thyroid indexes (TSH and thyroxine), and steroid hormone levels.…”

“…Importantly, thyroid hormones increase the response of the beta-adrenergic receptor to norepinephrine, which may serve as an adaptive mechanism of neuromodulation (Whybrow and Prange, 1981;Dratman and Gordon, 1996). More specifically, low TSH levels are also associated with elevated steroid hormone levels within the hypothalamus-pituitary-adrenal axis (van Haasteren et al, 1996). Increased levels of cortisol, which is part of this circuitry, may result in hippocampal cell loss and impair episodic memory performance (Lupien et al, 1994).…”

Dietary salt modulates the adrenocortical expression of p450 11beta‐hydroxylase in mice

“…Many studies have reported that food deprivation or restriction elevates plasma glucocorticoid levels (GarciaBelenguer et al, 1993;Kiss et al, 1994;van Haasteren et al, 1996). Furthermore, Chang et al (2002) reported that food deprivation enhances enzyme activity of P450 11beta and elevates plasma corticosterone level.…”