Chung-Hsiu Wu

Metabolism of free and sulfoconjugated DHEA in brain tissue in vivo and in vitro.

Abstract Two rhesus monkey brains were perfused in vivo either with 14C-DHEA (dehydroepiandrosterone) and 3H-DHEA sulfate or with 3H-DHEA. Plasma from the jugular vein and the brain were analyzed for free and conjugated metabolites. Many more free than sulfoconjugated steroids were withdrawn from the blood. These were not stored to a large extent. Up to 16% of DHEA were metabolized to ring D hydroxylated Δ5-compounds. When fresh human fetal brain was incubated with 3H-DHEA, 5.9% of the free steroids were sulfurylated. 30% were converted mainly to ring D hydroxylated Δ5-metabolites.

Estrogen formation in vitro by fetal liver, fetal adrenal gland, and placenta of early human pregnancy

Abstract Fetal liver and adrenal tissue and placental tissue were incubated in the presence of dehydroepiandrosterone-7α- 3 H. Fetal adrenal and liver tissue were also incubated in combination with placental tissue with the same precursor. Free and conjugated estrogens were analyzed in each incubate. Placental tissue alone formed small amounts of estriol from DHA. Fetal adrenal gland was unable to covert DHA to estrogens; however, if placental tissue was added, estriol was formed. Fetal liver was able to synthesize estrogens from DHA. When placental tissue was combined with liver, estrogens, especially estriol, were increased in free and conjugated forms.

Blood Flow to the Reproductive Organs of the Estrus Rabbit

The average blood flow to the ovaries, fallopian tubes, uterine horns and vagina of estrus rabbits was 1.40 ± 0.14, 1.44 ± 0.13, 0.75 ± 0.06, 0.30 ± 0.04 ml/min/g of tissue, respectively. There was no differences between the right and left organs. Ligation of the ovarian artery resulted in 80–90% decrease in blood flow to the ovary and oviduct, but recovery occurred within 1 and 6 days for the ovary and oviduct, respectively. There was no effect on the uterus and vagina. Ovulatory response to HCG occurred within 1 day and pregnancy after 6 days following ligation.

Endocrine basis for ovulation induction.

The endocrinology involved in spontaneous ovulation is reviewed and endocrine changes observed following treatment with some ovulation-inducing agents are discussed. The hypothalamus controls pituitary function. A gonadotropin-releasing hormone (GnRH) or luteinizing hormone-releasing hormone (LH-RH) has been isolated in the hypothalamus and identified chemically as a decapeptide. Synthetic GnRH has been produced. A balance among the hypothalamus pituitary and ovary controls the rhythmic ovulatory cycle. Radioimmunoassay for gonadotropins and for steroid hormones makes it possible to determine daily blood hormone concentrations. The hormones show distinct individual patterns and are mutually interrelated. Known details of hormone activities are given. Clinical induction of ovulation is possible by simulating natural phenomena. Use of clomiphene citrate (Clomid) is successful in producing ovulation in 80-90% of cases by conception follows in only 30-40%. Large amounts of androgens both testosterone and androstenedione are secreted from the ovary during Clomid therapy. This may play a significant role in reproductive failure with Clomid treatment. Human menopausal gonadotropin (HMG) such as Pergonal and Humegon improves the outcome of ovulation induction in patients with hypogonadotropic infertility. Estrogen may be used as an adjunct to Clomid therapy. Corticosteroid therapy has bee n found to suppress ovarian androgen secretion but the success rate in o vulation induction is low. L-Dopa therapy is effective in suppressing p ituitary prolactin. Its use may be successful in the treatment of patients with amenorrhea-galactorrhea. Ovulation has been reported in such cases. Growth hormone and carbohydrate matabolism may be changed. Br-ergocryptine therapy is also useful in the treatment of amenorrhea-galactorrhea by decreasing prolactin secretion from the pituitary. Induction of ovulation with LH-RH or GnRH has been relatively low. Prostaglandin therapy has been shown to produce ovulation in animal experiments. Its use in humans might produce unwanted side effects. Ovulation is usually confirmed by urinary increase in pregnanediol or plasma progesterone determination of Days 6-9 and by biopsy of secretory endometrium. Other better tests are too costly for frequent use. Daily urinary estrogen excretion seems a reasonable monitor in attempted induction of ovulation. Plasma estrogen levels may be of value in monitoring Clomid therapy in particular in determining when adjunctive HCG therapy is indicated.

Neutral steroid metabolites of dehydroepiandrosterone-7α-3H in human ovarian tissues

Abstract The metabolism of dehydroepiandrosterone-7α- 3 H by human ovarian tissues was studied by incubating slices of cortical stroma and corpora lutea of pregnancy. In the stroma the major metabolites of DHA were other androgens. A larger turnover of DHA occurred with luteal tissues and estrogens were the major metabolites. The isolation of Δ5-androstenediol, androstenedione and testosterone in all incubations suggests alternate pathways for the metabolism of DHA in both cortical stroma and corpora lutea.

Estrogen formation in vitro by fetoplacental tissues of midpregnancy

Abstract Midterm placenta and the placenta plus fetal tissues, including adrenal, liver, ovary, lung, kidney, and skin, were incubated separately with dehydroepiandrosterone (DHA)-7α- 3 H. Estrone, estradiol-17β, and estriol were identified in each incubate. The midterm placenta was active in converting DHA to estrone (40.9 per cent) and estradiol (16.3 per cent). The conversion of DHA to estriol was much lower (0.40 per cent). In the incubate of placenta plus fetal liver, the estriol yield was definitely higher (18.3 per cent) than that of other incubates. The conversion of DHA- 3 H to estrogens in other incubates of fetal tissues in combination with placenta or placenta alone was not remarkably different. These findings suggest that the fetal liver in association with the placenta plays an important role in estriol formation during midterm pregnancy.

Metabolism of Estradiol-17β-4-14C in a Non-Pregnant Rhesus Monkey.

Summary The metabolism of estradiol-17β-4-14C was studied in a rhesus monkey during the follicular stage of the menstrual cycle. The major portion of the injected dose was excreted in the urine during the first 24 hours as glucuronosides. Estradiol-17β and estrone were the principal radioactive estrogens found in this fraction of the urine. Smaller amounts of the radioactivity were identified as estriol and 16-epi-estriol.

Metabolism in vitro of dehydroepiandrosterone-7α-3H by human midterm fetal tissue

Abstract Fetal tissues at midgestation were found to have Δ 5 ,3β-ol steroid dehydrogenase activity. The conversion of dehydroepiandrosterone-7α- 3 H to androstenedione occurred in all tissues except liver and was highest in the gastrointestinal tract and testes. Testosterone was found mainly in the free fraction of the fetal testes, but it was also present in the glucuronide and sulfate fractions. Dehydroepiandrosterone-7α- 3 H was extensively sulfoconjugated by all tissues except fetal testes and skin, which suggests that this steroid might be conjugated with glucuronic acid in the fetus at midpregnancy.