As stated in the introduction by R. A. Peters, the purpose of this issue of the British Medical Bulletin "is to present a cross section of the research now in progress in this field of membranes." Although the coverage of the field is by no means complete, this purpose is achieved reasonably well in a series of short and concise reviews by investigators who are actively working on the problems they discuss. Various aspects of the structure and function of both cytoplasmic and plasma membranes are considered. The general areas discussed include chemistry and ultrastructure of membranes together with consideration of possible molecular organization, immuno-logical reactions and effects of pharmacologically active compounds, some aspects of transport across plasma membranes and mitochondrial membranes , and membrane function in excitable tissues. The articles are not, by and large, detailed expositions in the field, but are designed to provide an up-to-date summary of the current status of a variety of problems, and most include a selection of references adequate to guide the interested reader to more detailed information. I do not, however, mean to imply that the articles are elementary; a novice in the field will find some of them rather difficult and perhaps too concise, but they can serve as a guide for further reading and to a better understanding of some of the important aspects of the role of membranes in cellular function. Those interested in a good summary of research in a fairly wide variety of areas relating to memilbranes will surely find this issue of the bulletin useful. The volume is composed of proceedings of a symposium on hypothalamic pituitary adrenal function held in London on the 22nd and 23rd of Febru-ary, 1967 under the joint sponsorship of the endocrine section of the Royal Society of Medicine, Ciba Horsham, and the Society for Endocrinology. The participants were basic scientists and clinical investigators who by invitation presented data obtained from a variety of experimental approaches in an endeavor to elucidate the interrelationships of this complex neuroendocrine system. Part I is primarily concerned with stimulation and inhibition of adreno-corticotrophin secretion by pituitaries of animal species. The questions of hypothalamic control, corticosteroid or ACTH negative and oestrogen positive feedback, extra hypothalamic inhibitory influences such as pineal and hind brain factors, the site of vasopressin action on ACTH secretion and the relation of stress-induced ACTH release to concomitant TSH secretion are examined in …

It has been shown that either adrenocorticotrophic hormone (ACTH) or the 11-oxygenated adrenal cortical steroids inhibit the hyaluronidaseenhanced spreading phenomenon in the rabbit and in the mouse.q 8 In view of the favorable influence of pregnancy on certain of the collagen diseases, it was of interest to determine whether chorionic gonadotrophin had any influence on this phenomenon. This was found to be the case, but in the course of these investigations it became apparent that the inhibition produced by this agent was probably due, not to the gonad-stimulating principle, but to a contaminant which exhibited many of the properties previously associated with ACTH from pituitary tissue. While this work was in progress, Jailer and Knowlton' published a paper in which the presence of ACTH-like activity in extracts of placenta was indicated. The present study is to be regarded as of a preliminary nature since many points concerning the nature of the adrenal cortical stimulating principle remain to be clarified.

Experiments indicating that epinephrine activates the adrenal cortex only when the pituitary gland is intacte"" have led to the suggestion that epinephrine may exert an action directly upon the secretory cells of the anterior hypophysis." At the same time, a number of other drugs, notably histamine,' have also been shown to bring about the release of ACTH, and this finding has tended to relegate epinephrine to the role of a nonspecific agent in the activation mechanism. This is true particularly since a series of reports published by Sayers and his associates' have demonstrated that the output of adrenocorticotrophic hormone is suppressed when the level of adrenal cortical hormones rises in the circulating blood-an observation which has suggested that the level of circulating cortical hormones controls the ACTH output of the pituitary in much the same manner that the level of estrogens influences the output of the follicle stimulating hormone. It may be noted, however, that histamine as well as many other drugs which stimulate the release of ACTH are known to cause also a rapid release of epinephrine from the adrenal medulla," so that the possibility remains that a variety of other drugs may exert their action through the epinephrine mechanism. Since stating the original hypothesis concerning the role of epinephrine in activating the pituitary-adrenal system,' Long and his associates have continued to study the specificity of the response and the mechanisms through which it is brought about. Their data appear to show that epinephrine does not activate the pituitary through any of its other metabolic actions on electrolyte or carbohydrate metabolism. While they confirm, in part, the work of Sayers and his colleagues, the data of Long, et al.," and of McDermott, et al.," suggest that epinephrine has a specific role and an action directly upon the pituitary gland. In order to attempt a correlation of the data available on the mechanisms controlling the secretion of ACTH, and to investigate further the role of epinephrine in this control, it seemed necessary to compare normal animals with animals which were unable to liberate endogenous epinephrine in

1. Homologous grafts of pituitary tissue to the anterior chamber of the eye of the hypophysectomized rat retain the ability to secrete ACTH, both spontaneously and in response to activation by epinephrine.

This chapter contains section titled: Conditions Associated with Augmentation of ACTH Secretion The Nature of the Effect of Epinephrine on Adrenal Cortical Secretion References

It has previously been shown that the injection of pure adrenotrophic hormone into rats is followed by a rapid fall in adrenal ascorbic acid, a slower fall in adrenal cholesterol, and an increase in liver glycogen.1,2,3 It has been found (unpublished experiments) that exposure of rats to such conditions as cold, scalds, or hemorrhage is also followed by a depletion of adrenal cholesterol and ascorbic acid. However, since the above stresses are without any effect on the adrenal cholesterol and ascorbic acid of hypophysectomized rats, it is evident that a release of adrenotrophic hormone from the anterior pituitary is a preliminary and necessary step in the adrenal cortical response to an increased need for cortical hormone. The factors, humeral or nervous, that are associated with stress and which lead to an increased secretion of adrenotrophic hormone are not known, but it would appear that one common denominator is an increased degree of activity of the sympathetic nervous system, with a consequent release of epinephrine. We have, therefore, investigated the effect of epinephrine on the cholesterol and ascorbic acid levels of normal and hypophysectomized rats. Methods. Male rats about 200 g in weight of either Sprague-Dawley or Yale strain were used for this investigation. Non-fasted animals were hypophysectomized by the parapharyngeal approach under ether anesthesia. They were used on the third postoperative day after a fast of 18 hours, while food was withheld from normal rats 24 hours before the experiment. A 4-hour course of injections was given subcutaneously to both groups. Every hour each animal received 0.02 mg/100 g of epinephrine in physiological saline. One hour following the last injection the rats were quickly anesthetized with nembutal. The adrenals were removed and weighed on a torsion balance.

DIRECT PARTICIPATION of the adrenal cortex in the hormonal control of carbohydrate metabolism has been the subject of vigorous debate for a number of years. The interest in this problem has centered not only on the interpretation of the alterations in carbohydrate metabolism that occur in adrenalectomiz;ed animals, but also on their relation to the function of the adrenal cortex. This problem would appear to be capable of a simple solution were it not for the fact that other changes follow adrenalectomy that at first sight appear to be of greater significance than the disturbances in carbohydrate metabolism that have been reported. There is now no doubt that many adrenalectomized animals suffer such widespread disturbances intheir water and electrolyte balance that their ultimate death can hardly fail to be associated with them.