Nicholas W. Fugo

Effect of alloxan diabetes on reproduction in the rat.

Summary and Conclusions The effects of alloxan diabetes on ovarian activity and pregnancy were studied in a series of 63 adult female rats. The development of permanent hyperglycemia resulted in an alteration of the normal estrous pattern, so that the intervals were greatly prolonged. Pregnancy progressed normally until about the twelfth day following which the fetus died and was slowly absorbed, The placentas were retained and were delivered on the day of parturition. The adequate treatment of the alloxan diabetes by insulin resulted in normal pregnancies and live litters delivered at term.

Effects of Various Sex Hormones on Excretion of Pregnandiol Early in Pregnancy.

Summary Diethylstilbestrol, testosterone proprionate and progesterone were administered to 15 patients with normal pregnancies in order to study the effect of these substances on progesterone metabolism and pregnandiol excretion. Diethylstilbestrol and testosterone when administered daily in large amounts over long periods during the first 16 weeks of gestation did not alter the normal excretion of pregnandiol. The administration of progesterone was followed by the prompt recovery of a considerable portion of the injected steroid as pregnandiol.

Does Administration of Diethylstilbestrol to Pregnant Women Result in Increased Output of Urinary Pregnanediol

Summary and Conclusions When diethylstilbestrol is administered to a woman during pregnancy, much of this material appears in the urine as a glucuronide. In the Venning method for the assay of urinary pregnanediol, all of the glucuronides are included in the final determination. Thus diethylstilbestrol glucuronide as well as pregnanediol glucuronide appears in the result obtained. The apparent rise in the urinary pregnanediol values obtained by the Venning method may be due to the ingested diethylstilbestrol which is conjugated and eliminated in the urine. The figures do not indicate an increased production of progesterone and resultant increased output of urinary pregnanediol. Increasing amounts of diethylstilbestrol are being used in the treatment of pregnancy complications. In most instances the theory behind this therapeutic measure is that this estrogen stimulates steroid production. If urinary pregnanediol is to be used as a measure of increased steroid metabolism the value of diethylstilbestrol is open to question. It is possible that diethylstilbestrol exerts a favorable influence on placental circulation or on early placental development. However, there is no evidence that it results in an increased production of progesterone if urinary pregnanediol is to be regarded as an index of progesterone metabolism.

A simplified method for the quantitative determinations on free pregnanediol excretion in pregnancy.

Summary A rapid, accurate colorimetric method for the quantitative determination of pregnanediol based on the methods of Venning, Talbot and Guterman is described. Serial determinations in normal pregnancy and pregnancy complications have been carried out in over 100 patients. Pregnanediol excretion in the last 28 weeks of the gestation can be used as a quantitative measure of uteroplacental circulation. During this period the placenta is the chief source of this urinary metabolite for corpus luteum activity wanes rapidly after the first trimester. Serial determinations in normal pregnancy and the complications of pregnancy may throw light on the adequacy of the placenta as the essential organ for the survival of the fetus.

Metabolism and Excretion of Estrone Sulfate Labeled with Radioactive Sulfur (S35)

Summary 1. Radioactive estrone sulfate shows no definite localization in any of the target organs following intravenous or subcutaneous injection into mature female rats in spite of marked estrogenic response. 2. Estrone sulfate is rapidly hydrolyzed in the body. 3. Estrone sulfate is excreted not only by way of the urinary tract but considerable amounts find their way into feces. We wish to thank Dr. Edward C. Reifenstein, Jr., and Ayerst, McKenna and Harrison for the labeled and non-labeled estrone sulfate which they generously supplied.

Relaxation of the Pelvic Ligaments of Castrate Hysterectomized Guinea Pigs Induced by Progesterone.

Haterius and Fugo 1 showed that in castrate female guinea pigs relaxation of the pelvic ligaments could be elicited by treatment with crystalline progesterone after preliminary conditioning with estrogens. These findings cast some doubt upon the existence of a separate relaxation hormone, or at least its indispensability in the process of pelvic relaxation. More recently Hisaw et al. 2 confirmed the ability of crystalline progesterone to relax the pelvic ligaments in the spayed and estrogenized guinea pig. But they reported that in castrates which were hysterectomized the estrogen-progesterone treatment did not induce relaxation. The authors concluded therefore that under the conditions of their experiments athe uterus is indispensable for the formation of relaxin. It would seem from this interesting report that the presence of the uterus in some unexplained way facilitates relaxation but is not a necessary factor in the development of this reaction. Similarly progesterone is not indispensable since relaxin alone produces relaxation in the estrogenized hysterectomized castrate. Surprisingly, however, the combination of two factors (uterus and progesterone) each shown to be nonessential, together give a positive reaction. It was not the intention of this study to analyze the complicated nature of this reaction. Rather it was thought necessary to reinvestigate our earlier conclusion, namely, that progesterone alone was sufficient to produce relaxation when given in combination with estrogen. Furthermore it occurred to us that perhaps the failure of Hisaw et al. to obtain relaxation in castrate hysterectomized guinea pigs might be due to a time factor since their experimental procedure consisted in the injection of 250 mg of estradiol on 4 consecutive days followed by a single injection of 5 to 10 mg of progesterone on the following day. Consequently 12 virgin guinea pigs weighing approximately 200 g were castrated and hysterectomized under ether anesthesia.

The effect of tubal ligation on ovarian function in the rat.

Summary and Conclusions 1. Young healthy female rats with normal estrous cycles when treated by simple bilateral ligation of the oviducts proximal to the uterus show prolonged periods of estrus. 2. When the distended capsule produced by this procedure is removed the animals resume normal estrous cycles. 3. The fluid obtained from the capsule contains estrogenic hormone as demonstrated by estrous smears in spayed females rats. 4 The noteworthy histological changes in the ovaries after 30 days of tubal ligation are marked follicle stimulation and the absence of new corpora lutea. After 90 days following ligation the ovaries become cystic, probably due to an inadequacy of the blood supply.