Raphael Kurzrok

Biochemical Studies of Human Semen.∗ II. The Action of Semen on the Human Uterus.:

Summary The same uterus may react to one semen by contraction; to another by relaxation. The same semen may contract one uterus and relax another. From this we may draw the tentative conclusions that certain types of sterility are sometimes due to the female, sometimes to the male. A study of the history of the patients from whom uterine strips were obtained throws an interesting light on our experiments. The uteri from the patients who give a history of successful pregnancy responded to fresh semen by relaxation, while uteri from women who gave a history of complete or long-standing sterility were always stimulated by semen. A tentative deduction is permissible : Uteri are of 2 kinds, receptive and rejective; semina are also of 2 kinds, stimulant and depressant. A large series of carefully selected cases will be studied, with the purpose of criticising these deductions. We wish to thank Professor Benjamin P. Watson for putting at our disposal the large clnical facilities of the Sloane Hospital and Vanderbilt Clinic.

Biochemical Studies of Human Semen and its Relation to Mucus of the Cervix Uteri

Summary 1. There is present in human semen a substance that dissolves human cervical mucus. 2. The properties of this lytic substance suggest that it is an enzyme. 3. Considerations are offered relating this substance to sterility and fertilization. 3. Considerations are offered relating this substance to sterility and fertilization. 4. Semen has a strong reducing action on thionin and the possible significance of this reaction is discussed. 5. The reduction phenomenon of semen may have a bearing on the oxidative processes following fertilization. 6. Semen contains neither oxidase nor glutathione.

Estrus-Inhibiting Effects of Inanition

The effects of complete and partial starvation upon the estrous cycle of adult female rats were studied. Smears from the vaginal mucosa were taken for at least 2 weeks before any experimental procedures were instituted. Seven groups of 5 rats each were used. One group was kept as control; 2 groups received no food or water, and another only water at the onset of starvation; the fifth group was starved intermittently so that the loss of weight was more gradual. The remaining 2 groups were starved completely without water until they died. Each animal was weighed daily. The water and food consumption of the groups fed was recorded daily. It was found that the animals in all the starved groups eventually showed complete inhibition of the estrous cycle, and that the inhibition was roughly related to the loss in body weight, as shown in the table. When the inhibition of the estrous cycle was complete, all but 2 groups were fed again, with resulting return to the normal cyclical changes in the vaginal mucosa. Experiments to Determine the Factors Involved. In analyzing the estrus-inhibiting effects of starvation, one must distinguish between an inability of the vaginal mucosa to respond to estrogenic hormone; and the possibility that the ovaries have ceased to produce the hormone during the period of inanition. If the latter be true, one must further distinguish between a primary failure of the ovary, and a failure of the pituitary gland to produce the gonadotropic hormone. It is conceivable that any or all of these factors may be involved. 1. The effect of estradiol monobenzoate upon the inanition anestrus. Two groups of 10 rats were starved completely for 6 days. On the day starvation was begun 4 of the 10 animals were in estrus; 3 were just entering the diestrous phase; 2 were in diestrus: and 1 was in proestrus.

Excretion of Estrin in Acne

On clinical grounds it has long been suspected that acne vulgaris is caused by some endocrine disturbance—presumably by disturbance of the gonads (Pick, 1 Hollander, 2 Schamberg, 3 Darier, 4 Bloch, 5 Stein, 6 and others). The appearance of acne usually coincides with the endocrine changes for the sexual maturity associated with puberty. Only in exceptional instances is there any evidence that these changes are abnormal as for example, the case cited by Bloch in which acne appeared in the first years of life when (owing to suprarenal tumor) sexual maturity was precociously developed. It seemed to the writers that evidence of normality would be tested by a study of the excretion of estrin and prolan in women with acne. Previous studies 7 have shown that normal women between the ages of sex maturity and the menopause excrete from 10 to 20 rat units of estrin per liter of urine throughout the menstrual cycle. Prolan is not found by the methods here employed in such cases. The urines of 34 young women who applied to Vanderbilt Clinic for treatment of acne were examined. The age range was 11 to 33 years, 21 being under 20 years of age. Estrin was determined by the method of Kurzrok and Ratner, 8 and prolan by the method of Zondek. 9 Ovarian hormone was completely absent in 27 of these cases, present in normal amounts (10-20 rat units) in 6 cases, and slightly positive in one case (4 rat units). Work has not progressed to a stage from which final conclusions can be drawn, and the results of treatment with preparations of ovarian follicular hormone and anterior pituitary prohormone will be reported later, but a number of patients who formerly excreted no hormone were found to be excreting hormone after treatment.

Studies Relating to Time of Human Ovulation. II. During Lactation

Conclusions Thirty lactating women studied during their postpartum period had 106 fairly regular cycles. Thirty-nine cycles were ovulatory in character, hence fertile. Forty-five cycles were anovulatory or sterile, hence the bleeding at the end of each cycle was not true menstruation for it did not come from a premenstrual endometrium. There were 22 cycles of doubtful interpretation, by which we mean that 10 or more days elapsed between the date of the biopsy and the onset of the next period of bleeding. Ovulation could, therefore, potentially occur between the date of biopsy and the onset of the flow. Forty-two to 63% of the lactating women who bleed at fairly regular intervals have anovulatory or sterile cycles.

Biochemical Studies of Human Semen. III. Factors Affecting Migration of Sperm Through the Cervix.

The viscous mucus which normally fills the canal of the cervix uteri presents a first barrier to the migration of spermatozoa from the vaginal lumen to the upper parts of the tract where fertilization occurs. When a mass of this mucus is exposed to the action of normal seminal fluid, the gross appearance is that of a lysis, with loss of viscosity and disintegration of the mass, apparently due to specific enzymic action. 1 This action is inhibited by the presence in the mucus of notable amounts of pus, leucorrheal cells, etc. When the contact-boundary between normal cervical mucus and a normal semen specimen containing motile sperm is examined under the microscope, there is seen a gathering of sperm at the mucus surface which seems to be greater than can be accounted for merely by random swimming of the sperm. There is no evidence, however, of any attraction-field of the mucus surface exerting any influence on the distribution of sperm in the seminal fluid except in a narrow zone along the contact of the fluid with the mucus. The sperm do not very readily enter the mucus mass, nor do they progress in it, once entered, as rapidly as they do when swimming in a perfectly fluid medium. When one or more have succeeded in penetrating the mucus, what appears to be a small halo of more fluid material in the mucus can frequently be seen about the head of the advancing sperm, suggesting “lysis” of the mucus mass, thus making possible the advance of the sperm. Frequently, when one or more have entered, others follow, like a phalanx of sperm, with very actively lashing tails, following the leaders, oriented in general in the same direction, appearing to move up a “channel” against a vigorous current formed by the swimming-motion of the tails of those ahead; at times several sperm are swept backward and out by this current.