Estradiol and the control of food intake

Variations in food and water intake in the normal and acyclic female rat.

This paper provides the reader with an overview of our current knowledge of hypothalamic-pituitary-thyroid feedback from a cybernetic standpoint. Over the past decades we have gained a plethora of information from biochemical, clinical, and epidemiological investigation, especially on the role of TSH and other thyrotropic agonists as critical components of this complex relationship. Integrating these data into a systems perspective delivers new insights into static and dynamic behaviour of thyroid homeostasis. Explicit usage of this information with mathematical methods promises to deliver a better understanding of thyrotropic feedback control and new options for personalised diagnosis of thyroid dysfunction and targeted therapy, also by permitting a new perspective on the conundrum of the TSH reference range.

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TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis

Two groups of weaned sheep weighing about 30 kg, one born in March and the other in September, were each divided into two and given ad libitum one of two pelleted diets, ruminant diet A or ruminant diet AA6. The March-born sheep commenced experiment in July and those born in September in January. The experiment continued for 4½ years. At intervals sheep were killed and the fat protein and ash contents of their digesta-free bodies determined.The voluntary intake of feed showed a seasonal periodicity with minima in the winter and maxima in summer. The amplitude was 30% in the 1st year and in subsequent years averaged 13%. Those given the higher quality diet (AA6) consumed slightly less than those given the poorer one.Mean daily feed intake averaged over 6-month periods from January to July and July to January was invariant with age during 4 years of observation. In this time the sheep increased in weight from about 30 kg to about 130 kg. There were, however, considerable differences between individual sheep in the amount of feed they habitually consumed.The body weight of the sheep increased and eventually plateaued. The asymptotic weight defined as A in the equation W = A–Be–kt, where W is weight at time t and B and k are constants, was related to the mean daily feed intake averaged over 6 months; mean daily feed intake measured over 6 months was proportional to a fractional power of body weight indistinguishable from 0·75, the interspecies power to which metabolism is proportional. Growth of wool during successive 6-month periods did not vary with age of animal but differed significantly between animals.Fasting metabolism of the sheep was 316 kJ/kg W0·75 for wethers and 336 kJ for rams.Analysis of the bodily composition data showed that over a range of digesta-free body weight from 46 to 130 kg it was not possible, on statistical grounds, to distinguish between linear relationships between body weight and its fat, protein, ash and water content, and allometric ones. The linear relationships had marginally smaller residual standard deviations and the regression coefficients show that the gain of the empty body in these sheep consisted of 68% lipid, 8% protein, 1% ash and 24% water. The lipid in the carcass accounted for 88% of the total lipid gain and half the accretion of protein and ash was in the carcass. These results confirm those of Searle, Graham & O'Callaghan (1972) based on tritium dilution which showed that post-puberal growth in sheep is of constant composition.The results of the metabolic studies are shown to be consistent with the growth studies.Growth to maturity, as affected by different hypotheses related to the determinants of maintenance energy expenditure and the regulation of appetite, was examined algebraically. It is shown that mature weight is the rate of feed intake divided by the rate of maintenance metabolism per unit weight, and for defined feeding systems the rate constant for the approach to mature weight is the rate of maintenance metabolism divided by the feed equivalent of unit gain.The implications of the results in terms of the measurement and prediction of feed intake and the use of metabolic body size as a scaling factor in comparative and genetic studies of growth are briefly discussed.

A study of the growth of sheep to maturity

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Abstracts of communications

1. The role of thyroid hormone as a feed-back at the hypothalamic level in the control of thyrotrophin (TSH) secretion and release has been investigated by estimating the plasma and pituitary TSH levels following intrahypophysial and intrahypothalamic thyroid autotransplants.

2. Thyroidectomized rats bearing thyroid autotransplants in the pituitary had a significantly lower (P < 0·001) plasma TSH than that of controls at 26° C but not at 4° C.

3. Thyroidectomized rats bearing thyroid autotransplants in the supraoptic area showed a significantly lower (P < 0·001) level of plasma TSH and higher pituitary TSH at 4° C but not at 26° C.

4. Study with both unilaterally and bilaterally thyroidectomized rats bearing thyroid autotransplants either in the pituitary or in the hypothalamus revealed that thyroxine feed-back operates at pituitary level in normal situations (26° C) and there exists a feed-back through higher centres, specifically the TSR secreting area of the hypothalamus, in situations demanding higher thyroid function, as in cold exposure.

J. N. Panda

Papers

Thyroxine feed-back on the regulation of thyrotrophin secretion