J. R. Hodges

Hypothalamic receptors influencing the secretion of corticotrophin releasing hormone in the rat

1. The production of corticotrophin releasing hormone (CRH) by the rat hypothalamus in vitro was studied in the presence and absence of various neurotransmitter substances and drugs which mimic or antagonize their actions.

The effect of betamethasone on circadian and stress-induced pituitary-adrenocortical function in the rat

1 Both the circadian and stress‐induced changes in plasma corticosterone concentration were abolished by the inclusion of betamethasone in the drinking water of rats. 2 Adrenal sensitivity to exogenous corticotrophin (ACTH) was unimpaired by the betamethasone treatment. 3 The normal circadian rhythm in plasma corticosterone returned within 1 day of withdrawal of the steroid, but the response to stress was normal only after 3 days. 4 The possible significance of these observations is discussed.

Ascorbic acid deficiency and pituitary adrenocortical activity in the guinea-pig

1 . Guinea‐pigs kept on a diet deficient in ascorbic acid lost weight and became moribund in about 24 days. 2 . The adrenal ascorbic acid concentration fell rapidly during the first 2 weeks, and the plasma corticosteroid concentration and 17‐oxogenic steroid excretion rose sharply in the third week of ascorbic acid deficiency. 3 . Both histamine and corticotrophin increased the plasma corticosteroid concentration when injected during the second week but failed to change the pre‐existing high concentration of the steroid in the third week of ascorbic acid deficiency. 4 . The observations confirm that ascorbic acid is not involved in corticoidogenesis and that scurvy is a severe stress which increases adrenocortical activity to such an extent that the rate of synthesis of corticosteroids is incapable of matching the rate of their release.

The effect of reserpine on hypothalamo-pituitary-adrenocortical function in the rat.

1 The effect of reserpine on hypothalamo‐pituitary‐adrenocortical (HPA) function in the rat was investigated by the use of direct and indirect indices of pituitary adrenocorticotrophic activity. 2 Administration of a single dose of the drug induced prolonged hypersecretion of corticotrophin (ACTH). 3 Corticotrophin release in response to the drug no longer occurred after repeated daily injections, indicating that some form of ‘adaptation’ occurred. 4 The increase in HPA activity normally caused by exposure to cold was prevented by reserpine once ‘adaptation’ to the drug had been produced. 5 Inhibition of stress‐induced ACTH release was due neither to depletion of pituitary stores of the hormone, nor to a corticosteroid feedback effect.

HYPOTHALAMO-PITUITARY ADRENOCORTICAL FUNCTION IN THE RAT AFTER TREATMENT WITH BETAMETHASONE

1 Hypothalamo‐pituitary‐adrenocortical (HPA) activity was suppressed in rats treated with betamethasone. 2 Recovery of normal HPA function occurred after corticosteroid withdrawal. 3 Although corticotrophin release was rapidly restored to its basal rate there was a delay in the return of the normal adrenocorticotrophic response to stress and normal adrenocortical function was evident only after the plasma adrenocorticotrophic hormone had reached ‘supra‐normal’ levels. 4 The physiological significance and possible clinical relevance of the results are discussed.

Suppression of adrenocorticotrophic activity in the ascorbic acid deficient guinea‐pig

1 Adrenocortical hyperactivity caused by a marked increase in circulating corticotrophin occurred in guinea‐pigs on a diet deficient in ascorbic acid. 2 Betamethasone prevented the rise in the blood ACTH concentration in scorbutic animals and also the increased steroid production per gramme adrenal tissue in vitro. It diminished the adrenal hypertrophy and partially suppressed the rise in plasma Cortisol. 3 Ninety minutes after the injection of ascorbic acid corticotrophin could no longer be detected in the plasma of scorbutic animals. 4 Neither the survival time nor the weight loss was affected by betamethasone treatment.

Recovery of hypothalamo-pituitary-adrenal function in the rat after prolonged treatment with betamethasone.

1 . Betamethasone caused growth retardation, adrenal atrophy and impaired hypothalamo‐pituitary‐adrenal (HPA) activity in the rat. 2 . In spite of the profound impairment, recovery of normal HPA function was rapid, but the growth retardation persisted. 3 . The ability of the pituitary gland to secrete basal corticotrophin (ACTH), recovered more rapidly and the adrenocorticotrophic response to stress less rapidly than the ability of the adrenal cortex to respond to ACTH. 4 . The degree of HPA suppression was not determined by the total dose of steroid. 5 . The possible significance of the results is discussed.

Hypothalamo-pituitary-adrenal function in the rat after prolonged treatment with cortisol.

1 Cortisol, administered subcutaneously every day for long periods, caused growth retardation, adrenal atrophy and impaired hypothalamo‐pituitary‐adrenal (HPA) function in the rat. 2 The growth rate and the functional activity of the HPA system gradually returned to normal after steroid withdrawal. 3 Normal adrenal sensitivity to corticotrophin returned more rapidly than normal pituitary corticotrophic function, suggesting that the initial impairment of HPA function was due both to reduced responsiveness of the adrenal gland to corticotrophin and failure of the pituitary gland to secrete the hormone.

A CYTOCHEMICAL BIOASSAY METHOD FOR THE DETERMINATION OF LUTEINIZING HORMONE IN BIOLOGICAL FLUIDS AND TISSUES

1 The ability of luteinizing hormone (LH) to alter the reducing activity of corpora lutea in rat ovarian sections has been exploited to develop a new cytochemical bioassay for the hormone. 2 Sections of ovaries, removed from mature rats during the second day of dioestrus, were incubated with either standard LH or samples diluted for assay, stained immediately for reducing potential and the intensity of the stain measured by scanning and integrating microdensitometry. 3 An inverse linear relationship existed between the density of the stain and the logarithm of the concentration of standard LH (68/40) and the dose‐response lines of serial dilutions of rat or human plasma were parallel with those of the standard. 4 The method was found to be accurate, specific, sensitive, precise and suitable for the determination of LH in the rat and in man.

Effect of prolonged treatment with tetracosactrin on hypothalamo-pituitary-adrenal function in the rat

1 The functional integrity of the hypothalamo‐pituitary adrenal (HPA) system was assessed in rats after prolonged treatment with tetracosactrin. 2 Adrenal size and sensitivity to corticotrophin were increased. 3 Both the circadian rhythm and the stress‐induced increase in HPA activity were inhibited. The circadian rhythm recovered before the response to stress. 4 Tetracosactrin given after betamethasone treatment delayed the return of a normal HPA response to stress. 5 Suppression of HPA activity appeared to be the result of a direct action of tetracosactrin and not entirely due to the elevations in the plasma corticosterone concentration which it caused.