M. Edward Davis

Hormones in human reproduction

In undergoing this life, many people always try to do and get the best. New knowledge, experience, lesson, and everything that can improve the life will be done. However, many people sometimes feel confused to get those things. Feeling the limited of experience and sources to be better is one of the lacks to own. However, there is a very simple thing that can be done. This is what your teacher always manoeuvres you to do this one. Yeah, reading is the answer. Reading a book as this hormones in human reproduction and other references can enrich your life quality. How can it be?Abstract Following the administration of progesterone labeled with carbon 14 at position 21 to a patient with a normal pregnancy about 70 per cent of the administered radioactivity was recovered from the urine, feces, and expired air (22.62 per cent, 29.74 per cent, and 18.56 per cent, respectively). The excretion of radioactive metabolites by the skin was minimal. At present we have not accounted for the remaining 30 per cent of the administered radioactivity, but it seems likely that part of it is stored in the fat compartments of the body for a considerable length of time. There was no relationship between the urinary recovery of radioactivity and the pregnant and nonpregnant state, nor the viability of the fetus. The metabolites in urine and feces consist mainly of conjugated steroids, as pregnanediol, pregnanolone, and other unknown compounds. The elimination of tagged carbon dioxide after the administration of C 14 -21-progesterone indicates an oxidation of the side chain of the progesterone molecule, resulting in the formation of such steroids as androstenedione and related compounds which have androgenic properties. Determinations of radioactivity in the blood plasma following the intravenous and intramuscular administration of the labeled hormone demonstrated a rapid disappearance of the free steroid from the circulation due to (1) a speedy conjugation with glucuronic acid and (2) rapid diffusion into body tissues, mainly into the fat compartment. In contrast to the high concentration of radioactivity in the fat, only moderate amounts of radioactivity were demonstrated in the myometrium and the decidua of pregnant patients. Extremely low concentrations of radioactivity were found in the endometrium of non-pregnant women during the pre- and postovulatory phases of the menstrual cycle, and no radioactivity was demonstrable in the atrophic endometrium of 2 patients. The absence of estrogenic activity seems to prevent the entrance of the hormone into the cells of the mucosal layer of the uterus. This observation provides direct evidence that estrogens must prepare the endometrial cells in order that progesterone can exhibit its progestational effect. Apparently, only minimal amounts of progesterone and/or its metabolites are necessary to exert its biological effects on the endometrium. Preliminary studies on the biosynthesis of estrogens in human pregnancy revealed that cholesterol as well as testosterone can serve as a precursor of estrone. In a patient with choriocarcinoma C 14 -4-progesterone was converted into radioactive estrone. The data which we have presented here complete another milestone in the very long experimental road toward our understanding of the metabolism and biosynthesis of the steroid hormones in mammalian reproduction. It becomes increasingly apparent that our thorough understanding of their role in the normal reproductive process must precede an intelligent approach to the solution of many problems in obstetrics and gynecology.

Hormones in human reproduction: Part II. Further investigation of steroid metabolism in human pregnancy☆☆☆★

Abstract Following the administration of progesterone labeled with carbon 14 at position 21 to a patient with a normal pregnancy about 70 per cent of the administered radioactivity was recovered from the urine, feces, and expired air (22.62 per cent, 29.74 per cent, and 18.56 per cent, respectively). The excretion of radioactive metabolites by the skin was minimal. At present we have not accounted for the remaining 30 per cent of the administered radioactivity, but it seems likely that part of it is stored in the fat compartments of the body for a considerable length of time. There was no relationship between the urinary recovery of radioactivity and the pregnant and nonpregnant state, nor the viability of the fetus. The metabolites in urine and feces consist mainly of conjugated steroids, as pregnanediol, pregnanolone, and other unknown compounds. The elimination of tagged carbon dioxide after the administration of C 14 -21-progesterone indicates an oxidation of the side chain of the progesterone molecule, resulting in the formation of such steroids as androstenedione and related compounds which have androgenic properties. Determinations of radioactivity in the blood plasma following the intravenous and intramuscular administration of the labeled hormone demonstrated a rapid disappearance of the free steroid from the circulation due to (1) a speedy conjugation with glucuronic acid and (2) rapid diffusion into body tissues, mainly into the fat compartment. In contrast to the high concentration of radioactivity in the fat, only moderate amounts of radioactivity were demonstrated in the myometrium and the decidua of pregnant patients. Extremely low concentrations of radioactivity were found in the endometrium of non-pregnant women during the pre- and postovulatory phases of the menstrual cycle, and no radioactivity was demonstrable in the atrophic endometrium of 2 patients. The absence of estrogenic activity seems to prevent the entrance of the hormone into the cells of the mucosal layer of the uterus. This observation provides direct evidence that estrogens must prepare the endometrial cells in order that progesterone can exhibit its progestational effect. Apparently, only minimal amounts of progesterone and/or its metabolites are necessary to exert its biological effects on the endometrium. Preliminary studies on the biosynthesis of estrogens in human pregnancy revealed that cholesterol as well as testosterone can serve as a precursor of estrone. In a patient with choriocarcinoma C 14 -4-progesterone was converted into radioactive estrone. The data which we have presented here complete another milestone in the very long experimental road toward our understanding of the metabolism and biosynthesis of the steroid hormones in mammalian reproduction. It becomes increasingly apparent that our thorough understanding of their role in the normal reproductive process must precede an intelligent approach to the solution of many problems in obstetrics and gynecology.

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.

American Gynecological Society Transactions of the Seventy-ninth Annual Meeting Washington, D.C., May 21–23, 1956Hormones in human reproduction: Part I: Metabolism of progesterone☆☆☆★

In undergoing this life, many people always try to do and get the best. New knowledge, experience, lesson, and everything that can improve the life will be done. However, many people sometimes feel confused to get those things. Feeling the limited of experience and sources to be better is one of the lacks to own. However, there is a very simple thing that can be done. This is what your teacher always manoeuvres you to do this one. Yeah, reading is the answer. Reading a book as this hormones in human reproduction and other references can enrich your life quality. How can it be?Abstract Following the administration of progesterone labeled with carbon 14 at position 21 to a patient with a normal pregnancy about 70 per cent of the administered radioactivity was recovered from the urine, feces, and expired air (22.62 per cent, 29.74 per cent, and 18.56 per cent, respectively). The excretion of radioactive metabolites by the skin was minimal. At present we have not accounted for the remaining 30 per cent of the administered radioactivity, but it seems likely that part of it is stored in the fat compartments of the body for a considerable length of time. There was no relationship between the urinary recovery of radioactivity and the pregnant and nonpregnant state, nor the viability of the fetus. The metabolites in urine and feces consist mainly of conjugated steroids, as pregnanediol, pregnanolone, and other unknown compounds. The elimination of tagged carbon dioxide after the administration of C 14 -21-progesterone indicates an oxidation of the side chain of the progesterone molecule, resulting in the formation of such steroids as androstenedione and related compounds which have androgenic properties. Determinations of radioactivity in the blood plasma following the intravenous and intramuscular administration of the labeled hormone demonstrated a rapid disappearance of the free steroid from the circulation due to (1) a speedy conjugation with glucuronic acid and (2) rapid diffusion into body tissues, mainly into the fat compartment. In contrast to the high concentration of radioactivity in the fat, only moderate amounts of radioactivity were demonstrated in the myometrium and the decidua of pregnant patients. Extremely low concentrations of radioactivity were found in the endometrium of non-pregnant women during the pre- and postovulatory phases of the menstrual cycle, and no radioactivity was demonstrable in the atrophic endometrium of 2 patients. The absence of estrogenic activity seems to prevent the entrance of the hormone into the cells of the mucosal layer of the uterus. This observation provides direct evidence that estrogens must prepare the endometrial cells in order that progesterone can exhibit its progestational effect. Apparently, only minimal amounts of progesterone and/or its metabolites are necessary to exert its biological effects on the endometrium. Preliminary studies on the biosynthesis of estrogens in human pregnancy revealed that cholesterol as well as testosterone can serve as a precursor of estrone. In a patient with choriocarcinoma C 14 -4-progesterone was converted into radioactive estrone. The data which we have presented here complete another milestone in the very long experimental road toward our understanding of the metabolism and biosynthesis of the steroid hormones in mammalian reproduction. It becomes increasingly apparent that our thorough understanding of their role in the normal reproductive process must precede an intelligent approach to the solution of many problems in obstetrics and gynecology.

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.

Distribution of Radioactivity in Human Maternal and Fetal Tissues Following Administration of C14-4-Progesterone.

Summary C14-4-progesterone was administered intramuscularly to pregnant women who were scheduled for therapeutic abortion. Distribution of radioactivity in maternal and fetal tissue removed at various time intervals following injections was determined. The highest concentration of radioactivity was found in the maternal fat. A rough calculation revealed that it contained about 17.7% of the administered radioactivity 12 hours. 33.7% 24 hours, and 19.6% 48 hours after administration of the labelled hormone. These findings indicate that progesterone and or its metabolites diffuse promptly from the blood circulation into the fat compartment of the body. Only moderate amounts of radioactivity were found in the myometrium and the decidua. the 2 principal target organs of progesterone. Low to moderate concentrations of radioactivity were detected in the organs which serve as principal sources of the hormone, the corpus luteum and the placenta. Radioactivity was present in all fetal tissues in relatively small amounts with the exception of the fetal brain, and the testes.SummaryC14-4-progesterone was administered intramuscularly to pregnant women who were scheduled for therapeutic abortion. Distribution of radioactivity in maternal and fetal tissue removed at various time intervals following injections was determined. The highest concentration of radioactivity was found in the maternal fat. A rough calculation revealed that it contained about 17.7% of the administered radioactivity 12 hours. 33.7% 24 hours, and 19.6% 48 hours after administration of the labelled hormone. These findings indicate that progesterone and or its metabolites diffuse promptly from the blood circulation into the fat compartment of the body. Only moderate amounts of radioactivity were found in the myometrium and the decidua. the 2 principal target organs of progesterone. Low to moderate concentrations of radioactivity were detected in the organs which serve as principal sources of the hormone, the corpus luteum and the placenta. Radioactivity was present in all fetal tissues in relatively small amo...

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.

A clinical study of stilbestrol

I N 1934 Cook, Dodds, Hewett, and Lawson reported on the estrogeni<+ activity of some condensed-ring compounds. Following this work, in 1938 Dodds, Goldberg, Lawson, and Robinson described the synthesis of dihydroxydiethyl stilbene, a chemical with marked estrogenic activity. They gave the name of stilhestrol to this new organic compound. Although a most potent estrogen, it is not related chemically nor in any other way to the naturally occurring estrogens. Careful biologic standardization indicates that 1 mg. of this new drug is equivalent in action to 25,000 international units of estronc. Other derivatives of stilbene have varying est,rogrnic action, but stilbestrol is the most potent of the group. Dodds and his associates, as well as a number of other investigators, have st,udied the estrogenic action of stilbestrol. These reports indicate that this organic drug will reproduce all the physiologic changes that can be induced by t,hc natural estrogens. The toxicity of t,he drug has been studied in laboratory animals and varies widely. Rabbits withstood 30 mg. per kilogram administered intravenously, although cats succumbed to t,his dosage. Guinea pigs arc unusually tolerant of t,hc drug, for they showed no effects from hugcb doses of 200 mg. per kilo. of body weight. Experiments with the prolonged administration of the drug to laboratory animals arc still under way. It is exceedingly important t,o determine l-he effect of small and moderate amounts administered at, frequent intervals over long periods of time for this mode of administration more nearly simulates the clinical use of the drug.

SYNERGISM AND ANTAGONISM OF SEX STEROIDS AS DETERMINED ON THE VAGINAL EPITHELIAL CELLS

Estrogens, androgens, or progestogens induce either proliferation of the vaginal epithelium or regressive changes, or they have no effect on the stage of proliferation.’ The type of epithelial reaction to a given hormonal stimulus is greatly dependent upon the stage of proliferation at the time of administration, the endocrinological condition of the patient, and individual variations in epithelial response? Cytological determinations of the specific epithelial response to administered steroids may be used in determining the proper mixture of estrogens and androgens, or estrogens and progestogens. The cytological response, however, is not always useful in determining the actual clinical effect of the substance: especially in dealing with androgens or progestogens.2