J. S. L. Browne

The significance of endocrine assays in threatened and habitual abortion

Abstract 1. 1. The physiology of normal pregnancy is discussed from the point of view of the endocrine factors involved. 2. 2. A study has been made of 35 cases of threatened or habitual abortion, and measurement of the excretion of prolan (chorionic gonadotrophic substance), total estrogens and sodium pregnandiol glucuronidate has been made in twenty-four-hour specimens of urine in these patients for varying lengths of time, in some patients throughout pregnancy. 3. 3. A theory of the underlying endocrine basis for abortion is presented. 4. 4. An attempt is made to evaluate progesterone therapy in such cases on a rational basis.

The contractions of the human uterus during the menstrual cycle

In each of four women with fairly normal ovarian and uterine function as shown by their ability to conceive, one or more cycles were fully studied; including pregnanediol assays, endometrial biopsies, and uterine tracings; a fifth was completely studied except that urinary assays were not done on every day; a sixth whose cycles were abnormal to the extent that she was unable to conceive was also studied and a seventh had tracings and biopsies done in one cycle but no pregnanediol assays were made. In each the uterus contracted more strongly and was much more greatly affected by pituitrin in the presence of the corpus luteum than during the follicle phase. An artificially produced cycle showed a similar increase in spontaneous activity and response to pituitrin after injection of 20 mg. of progesterone. Two cases of anovulatory cycles showed spontaneous activity and response to pituitrin characteristic of the follicle phase.Abstract In each of four women with fairly normal ovarian and uterine function as shown by their ability to conceive, one or more cycles were fully studied; including pregnanediol assays, endometrial biopsies, and uterine tracings; a fifth was completely studied except that urinary assays were not done on every day; a sixth whose cycles were abnormal to the extent that she was unable to conceive was also studied and a seventh had tracings and biopsies done in one cycle but no pregnanediol assays were made. In each the uterus contracted more strongly and was much more greatly affected by pituitrin in the presence of the corpus luteum than during the follicle phase. An artificially produced cycle showed a similar increase in spontaneous activity and response to pituitrin after injection of 20 mg. of progesterone. Two cases of anovulatory cycles showed spontaneous activity and response to pituitrin characteristic of the follicle phase.

Urinary excretion of adrenal cortical steroids.

It has become apparent in recent years, through the work of many investigators, that the adrenal cortex has a variety of functions. The substances so far derived from it may be roughly divided into three groups: (1) compounds which act mainly on electrolyte metabolism; ( 2 ) compounds which affect protein and carbohydrate metabolism, and (3) compounds which have properties of the sex hormones. Into the last group fall the estrogens, progesterone, and the androgens. The latter also affect protein metabolism. Metabolites of these various adrenal hormones are excreted in the urine and an attempt has been made to correlate these urinary substances with their possible precursors in the gland or with definite types of adrenal function. In man, two groups of urinary steroids have been associated with adrenal metabolism, namely, the 17-ketosteroids and the glycogenic corticoids. The first group, the 17-ketosteroids, are characterized by the facts that they have a carbonyl group a t C-17 and give a typical color reaction with alkaline dinitrobenzene. They have been associated with the adrenal, because they are found to be increased in cases of adrenal tumor and decreased in cases of hypofunction of the adrenal. In the male, the 17ketosteroids are derived from both the adrenal and the testis, whereas, in the female, they are entirely of adrenal origin. The adrenal precursors of these substances have not yet been identified, but they are considered to be associated with the androgenic function of the adrenal, and to have an anabolic effect on body protein. The glycogenic corticoids differ from the 17-ketosteroids in that they possess the same biological activity as the corticosterones, i.e., they are capable of prolonging the life of adrenalectomized animals and will cause an increase in liver glycogen when administered to fasting adrenalectomized animals. They are readily extractable from urine with chloroform or ethylene dichloride, are strongly reducing substances, and are heat labile. They are associated with that group of adrenal substances which are concerned with carbohydrate metabolism. . The urinary corticoids have been assayed by the method of Venning, Kasmin, and Be1l.l It is a bioassay based upon the ability of these hormones to cause a deposition of glycogen in the livers of adrenalectomized fasted mice. Briefly, the assay is carried out in the following manner: The urinary extract is prepared by acidifying a &hour specimen of urine to pH 1 and extracting it with ethylene dichloride or chloroform. After distilling off the solvent, the residue is taken up in chloroform and the solution is extracted with N/10 alkali and water. The chloroform is evaporated off and the residue obtained is dissolved in a small amount of alcohol and is finally made up into an extract containing 10 per cent alcohol