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Biomedical subjects

R V Haning

Publications and source records attributed to R V Haning.

At least 37 records · Page 2Linked to original sources
PubMed1991

Metabolism of dehydroepiandrosterone sulfate (DS) in normal women and women with high DS concentrations.

In order to determine the contribution of serum dehydroepiandrosterone sulfate (DS) to estrone (E1) production in normal women and the effect of chronic elevation of the serum DS concentration on DS metabolism, four normal women and four women with high endogenous serum DS were infused with [3H]DS and [14C]E1 or [14C]testosterone for 6 h. Blood samples were analyzed for radioactivity as DS, dehydroepiandrosterone (D), androstenedione, testosterone, and dihydrotestosterone. Urine was collected for analysis of creatinine, 17-ketosteroids (17-KS), and radioactivity as estrone (E1). The serum DS of 12.4 +/- 1.44 mumol/L (mean +/- SE) in the group with high DS was higher than that of 3.96 +/- 1.0 mumol/L (1.46 +/- 0.37 micrograms/mL) in the normals (P less than 0.005). Those with high DS also had increased 17-KS (13.2 +/- 2.0 vs. 5.68 +/- 0.68 mg/day, P less than 0.025) and a higher blood production rate of DS (PBDS) (126 +/- 21 (n = 3) vs. 54.3 +/- 13.8 mmol/day, P less than 0.05) but a lower MCRDS (10.94 +/- 0.61 (n = 3) vs. 13.8 +/- 0.27 L/day, P less than 0.01) than that in normals. In the four normal women the fraction of infused DS converted to estrone ( [rho]BMDS E1) was 0.00078 +/- 0.00018, the amount of E1 produced from serum DS was 41.3 +/- 15 nmol/day, the basal plasma E1 was 102 +/- 18 pmol/L, the MCRE1 was 1340 +/- 181 L/day, the value for blood production of E1 (PBE1) was 129 +/- 12 nmol/day, and the portion of E1 derived from DS was 30.4 +/- 9.4%. Correlation analysis of the data from these eight subjects showed that 17-KS, PBDS, and the serum DS were all correlated with body surface area, body weight, and ponderal index and that 17-KS excretion, PBDS, and serum DS were all correlated with one another. The most important predictors of 17-KS excretion were serum DS (P less than 0.001) and the ponderal index (P less than 0.05).

17-Ketosteroids↗
PubMed1990

Steroid sulphatase activity in the human ovarian corpus luteum, stroma, and follicle: comparison to activity in other tissues and the placenta.

Steroid sulfatase activity was measured in 89 human samples, using dehydroepiandrosterone sulfate (DHEAS) as substrate. The lowest activity was that of follicular fluid which was significantly lower than that of other tissues tested (each P less than 0.01). The steroid sulfatase activity of ovarian tissue taken collectively (corpus luteum, stroma, and follicles) was higher than that of other tissues taken collectively (abdominal skin, uterus, and fallopian tube) (P less than 0.001), and the steroid sulfatase activity of either the follicle (P less than 0.01) or the stroma (P less than 0.05) was significantly greater than that of the corpus luteum. The geometric mean steroid sulfatase activity of the placenta was significantly higher than other tissues tested (each P less than 0.01) and was 22-fold higher than that of the follicle, the tissue with the next highest activity. These data indicate that the human ovary (particularly the stroma and follicle) is capable of utilizing DHEAS, an adrenal product, as a substrate for production of other androgens such as dehydroepiandrosterone (DHEA), androstenedione, and testosterone.

Arylsulfatases↗
PubMed1990

Neonatal intracranial choriocarcinoma.

A 1-month-old infant died from extensive intracerebral hemorrhage due to a metastatic choriocarcinoma to the brain that presumably originated in the placenta. The clinical course was characterized by hyperbilirubinemia, repeated episodes of seizures, and intracranial hemorrhage. A computed tomographic scan revealed a large vascular mass in the left parieto-occipital region and a small lesion in the left frontal lobe. The placenta was expelled during the delivery and was not examined. In view of the high level of maternal human chorionic gonadotropic hormone and the autopsy finding of metastasis, we presumed that the mass was a metastatic choriocarcinoma that had originated in the maternal placenta. To our knowledge, only one previous instance of this phenomenon has been reported.

Brain Neoplasms↗
PubMed1989

Effects of fetal sex and dexamethasone on preterm maternal serum concentrations of human chorionic gonadotropin, progesterone, estrone, estradiol, and estriol.

The serum human chorionic gonadotropin concentration for the 43 female-bearing gestations was significantly higher (geometric mean 15,603 mIU/ml; 95% confidence interval 12,337 to 19,733) than that for 26 male-bearing pregnancies (geometric mean 8902 mIU/ml; 95% confidence interval 6288 to 12,596), p = 0.0087. The mean gestational age was 32 +/- 2.4 weeks (mean +/- SD). There was no significant difference between male- and female-bearing pregnancies for progesterone, cortisol, estrone, estradiol, estriol, or gestational age. In 19 placebo-treated pregnancies and 14 dexamethasone-treated pregnancies with a mean gestational age of 31.5 +/- 2.7 weeks, there was no significant change from the baseline value observed for either maternal serum human chorionic gonadotropin level or maternal serum progesterone level at 42 hours after institution of treatment. In the dexamethasone-treated subjects the geometric mean was reduced to 20% of baseline for cortisol; 42% of baseline for estrone; 30% of baseline for estradiol; and 41% of baseline for estriol (all p less than 0.001).

Chorionic Gonadotropin↗
PubMed1989

Metabolic clearance rate (MCR) of dehydroepiandrosterone sulfate (DS), its metabolism to dehydroepiandrosterone, androstenedione, testosterone, and dihydrotestosterone, and the effect of increased plasma DS concentration on DS MCR in normal women.

The combined infusion of [3H]dehydroepiandrosterone sulfate [( 3H]DS) and [14C]estrone (E1) for 6 h in four normal women in the follicular phase of the cycle demonstrated values of 13.77 +/- 0.27 L/day (mean +/- SE) for the DS MCR (MCRDS) and 1343 +/- 206 L/day for MCRE1. The fraction of DS metabolized to dehydroepiandrosterone (D), [rho]DS-D, was 0.285 +/- 0.044, and the fraction of D arising from DS (delta D) was 0.318 +/- 0.096, determined using isotopic techniques. Raising the plasma DS concentration by 8.6 micrograms/mL (23 mumol/L) by infusing DS iv increased the MCRDS to 24.49 L/day in the first subject, and raising the plasma DS by 11.40 +/- 0.33 micrograms/mL (30.94 +/- 0.90 mumol/L) in the next three subjects raised the MCRDS to 35.7 +/- 1.3 L/day (P less than 0.01) without changing the MCRE1. The increase in MCRDS produced by increasing plasma DS makes it difficult to accurately measure the MCRDS in effect at the subject's endogenous plasma DS concentration by infusion of nonisotopic DS. Determination of the fractions of D, androstenedione (delta delta 4A), and testosterone (T) arising from DS using the increase in the plasma concentrations of these steroids produced by infusion of nonisotopic DS gave the following estimates: delta D = 0.262 +/- 0.042, delta delta 4A = 0.089 +/- 0.046, and delta T = 0.273 +/- 0.14.

Adult↗
PubMed1989

Diagnosis and resection of an oral contraceptive-suppressible Sertoli-Leydig cell tumor with preservation of fertility and a 7-year follow-up.

A 21-year-old white woman presented with virilization, hirsutism, and acne of 1.5 years' duration. Endocrine testing demonstrated complete suppression of serum testosterone, from 5.3 to 0.6 ng/mL, and serum androstenedione, from 4.7 to 1.7 ng/mL, after oral administration of 50 micrograms of mestranol and 1 mg of norethindrone for 21 days. No suppression of either steroid was produced by dexamethasone, whereas serum dehydroepiandrosterone sulfate was suppressed from 5.2 to 1.9 micrograms/mL. A left salpingo-oophorectomy was performed for a 3 x 4-cm Sertoli-Leydig cell tumor of intermediate differentiation. Intraoperative studies demonstrated that the tumor secreted testosterone, androstenedione, 17 alpha-hydroxyprogesterone, and estradiol, but not dehydroepiandrosterone sulfate. These findings support the thesis that hormonal manipulation tests cannot differentiate between adrenal and ovarian virilizing tumors. Nor does the oral contraceptive suppression of testosterone secretion exclude an ovarian malignancy. The patient remains free of recurrence after 7 years.

Adult↗
PubMed1988

Effects of fetal sex, stage of gestation, dibutyryl cyclic adenosine monophosphate, and gonadotropin releasing hormone on secretion of human chorionic gonadotropin by placental explants in vitro.

Explants from 16 term and 6 midtrimester placentas were cultured for 6 days. Statistically significant increases in secretion of human chorionic gonadotropin occurred in control medium cultures of both term and midtrimester explants during the 6-day culture period (p less than 0.01). Statistically significant increases in secretion of human chorionic gonadotropin were produced by 2 mmol/L dibutyryl cyclic adenosine monophosphate in both the term (p less than 0.01) and the midtrimester (p less than 0.01) explants. There was no effect of gonadotropin releasing hormone. The ratio of human chorionic gonadotropin secretion from midtrimester explants to that from term explants varied under different conditions, dropping from twentyfold in day 1 cultures to elevenfold for maximum secretion produced after culture in control medium for up to 6 days. A further drop in the ratio to fourfold was observed for the maximal response to 2 mmol/L dibutyryl cyclic adenosine monophosphate treatment. Explants from term female infants produced significantly more human chorionic gonadotropin than those from term male infants (p less than 0.05), but the sex difference disappeared after stimulation with 2 mmol/L dibutyryl cyclic adenosine monophosphate.

Bucladesine↗
PubMed1988

Lipid and glucose metabolism in human placental culture.

Placental culture models have been used to increase the understanding of endocrinology and pathophysiology in pregnancy. This article describes glucose and lipid metabolism in several of these models. Of special interest is the availability of arachidonic acid for the production of prostanoids. Ten placentas were collected at the time of cesarean section in term pregnancies without labor. Minced villous tissue was incubated for 48 hours in media with a glucose concentration of 100, 200, or 500 mg/dl. Tissue was dispersed in the media or was left as a single clump during the incubation. Glucose levels in the culture media were measured at 8, 20, 32, and 48 hours. Tissue lipid levels were measured before and after incubation in seven placentas. At 8 hours, glucose utilization ranged from 2.38 +/- 0.40 to 9.44 +/- 1.22 mumol/gm tissue/hr (mean +/- SEM). By 48 hours the cumulative glucose utilization ranged from 1.56 +/- 0.09 to 6.87 +/- 0.38 mumol/gm tissue/hr. Tissue lipid analysis showed most of the fatty acids to be in the phospholipids initially (4477 +/- 179 micrograms/gm tissue). Subsequent to incubation for 48 hours, phospholipid levels fell to a range of 2686 +/- 90 to 3466 +/- 157 micrograms/gm tissue in various culture conditions (p less than 0.005 compared with initial values). Whereas phospholipid levels decreased during incubation, levels of triglycerides and nonesterified fatty acids increased significantly in placental tissue. Arachidonic acid, the precursor of prostaglandins, thromboxane, and prostacyclin, makes up about one quarter of the fatty acid in the initial placental phospholipid. Arachidonic acid follows the pattern of total fatty acids during incubation; it is released from phospholipid and is converted to nonesterified fatty acid and triglyceride. We may conclude from this study that each placenta has a unique glucose utilization rate and a unique capacity to produce triglyceride. In tissue culture, arachidonic acid is released to its nonesterified state much more quickly than it can be converted to prostanoids by cyclooxygenase. The choice of initial glucose concentration, tissue preparation (dispersed in media or left as single clump), and time of incubation all may determine the rate of glucose metabolism, the rate of phospholipid breakdown, the rate of triglyceride production, and the quantity of nonesterified arachidonic acid in placental tissue culture.

Arachidonic Acids↗
PubMed1985

Evaluation of intra-amniotic administration of 120 gm of urea with 5 mg of prostaglandin F2 alpha for midtrimester termination of pregnancy between 20 and 24 weeks' gestation.

The occasional finding of signs of life in fetuses delivered following intra-amniotic administration of 80 gm of urea and 5 mg of prostaglandin F2 alpha suggested that the dose of 80 gm of urea was inadequate beyond the nineteenth week. Protocol modifications were made, and the metabolic effects of intra-amniotic administration of 120 gm of urea used beyond the nineteenth week were compared to those of the 80 gm dose of urea used in patients prior to the twentieth week. The 120 gm urea dose was well tolerated. The peak blood urea nitrogen (at 4 hours after instillation) was higher with 120 gm of urea (36.4 mg/dl) than with 80 gm of urea (24.6 mg/dl) (p less than 0.05). Small decreases in the platelet count (14% of control) and serum fibrinogen (11%), sodium (2%), potassium (7%), and carbon dioxide (11%) levels and a 5% increase in peak serum osmolality were found. Following the change in protocol, fetal heart activity has been absent at 3 hours after instillation in all cases less than 24 weeks from the last menstrual period.

Abortion, Induced↗
PubMed1985

Maternal serum progesterone, 17 beta-estradiol and estriol are increased in pregnancies which follow treatment with human menopausal gonadotropins: effects of multiple gestation and maternal endocrine status.

A high incidence of premature labor, incompetent cervix and fetal wastage occurs in multiple gestations which follow treatment with human menopausal gonadotropins (HMG). In order to determine the effect of treatment with HMG on hormone secretion in human pregnancy, progesterone (PROG), 17 beta-estradiol (E2), estriol (E3) and human chorionic gonadotropin (hCG) were determined by radioimmunoassay in 341 serum specimens from 229 normal singleton pregnancies and in 79 serum specimens from 20 pregnancies following induction of ovulation with HMG in women with either hypothalamic amenorrhea (HA) or the polycystic ovary syndrome (PCO). Fitting equations were found for the log transformed normal values and the residuals were obtained by subtraction of the predicted normal values from the log transformed values observed in the HMG pregnancies. In pregnancies which followed treatment with HMG, PROG and E2 were initially elevated above normal. As pregnancy progressed, the deviation from normal became proportionately less. PROG (P less than 0.025) was lower and E2 (P less than 0.025) and E3 (P less than 0.05) were higher in PCO pregnancies than in HA pregnancies. Multiple gestation produced increases in PROG (P less than 0.005), E2 (P less than 0.005) and E3 (P less than 0.001) in comparison to singleton pregnancies.

Amenorrhea↗
PubMed1985

A syndrome of chronic renal failure and XY gonadal dysgenesis in young phenotypic females without genital ambiguity.

A case of XY gonadal dysgenesis with renal failure is presented. Diagnosis was delayed four years post renal transplantation. A uterus, fallopian tubes, and vagina were present with a combined gonadoblastoma and dysgerminoma found in the right streak gonad. Six other similar cases have been reported, including concordance in a pair of monozygous twins. Because of the risk of gonadal malignancy, the serum FSH concentration should be determined in phenotypic females with primary amenorrhea and chronic renal disease. Due to a physiologic reduction in the serum FSH concentration in agonadal individuals between 5 and 11 years of age, a karyotype may be required to detect affected individuals during this interval. Gonadectomy should be performed in all cases of XY gonadal dysgenesis. A urinalysis and serum creatinine concentration should be obtained in girls presenting with XY gonadal dysgenesis. The serum FSH concentration and karyotype should be determined in females presenting with congenital nephrotic syndrome.

Adolescent↗
PubMed1985

Effects of dibutyryl cyclic AMP and gonadotropin-releasing hormone added prior to filter sterilization of the media and variation in oxygen partial pressure on output of human chorionic gonadotropin from term placental explants.

The effect of 2 mM dibutyryl cyclic AMP (dbcAMP) and 10 and 100 micrograms/ml gonadotropin-releasing hormone (GnRH) added prior to filter sterilization and of varying oxygen partial pressure (5, 20, and 95% oxygen) were evaluated using explants from each of 4 placentas on each of 6 days of culture. There were significant differences between placentas on days 1 and 2 of culture (both p less than 0.025), and day 4 (p less than 0.05), but there were no effects of GnRH or varying oxygen partial pressure on output of human chorionic gonadotropin under the conditions evaluated.

Bucladesine↗
PubMed1985

Role of dehydroepiandrosterone sulfate as a prehormone for ovarian steroidogenesis.

The endocrine effects of induction of ovulation with menotropins were studied in 43 patients: 11 with hypothalamic amenorrhea and 32 with the polycystic ovary syndrome. Patients with polycystic ovary syndrome had higher base-line values of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 beta-estradiol, dehydroepiandrosterone sulfate, testosterone, and a higher testosterone-free index than those with hypothalamic amenorrhea. During treatment with menotropins, patients with polycystic ovary syndrome had higher values of serum LH, prolactin, dehydroepiandrosterone sulfate, testosterone, percent free testosterone, testosterone-free index, and body weight than those with hypothalamic amenorrhea; serum FSH, dose of menotropins per kilogram body weight, and total follicular volume were higher in patients with hypothalamic amenorrhea than in those with polycystic ovary syndrome. Multiple linear regression after log transformation demonstrated that the testosterone-free index was predicted statistically by total ovarian volume and dehydroepiandrosterone sulfate and that serum 17 beta-estradiol was predicted statistically by total ovarian volume and testosterone-free index. Adding dexamethasone to menotropins in six patients with polycystic ovary syndrome produced significant decreases in 17 beta-estradiol, dehydroepiandrosterone sulfate, testosterone, and testosterone-free index. Higher concentrations of endogenous serum LH and dehydroepiandrosterone sulfate in patients with polycystic ovary syndrome in comparison with those with hypothalamic amenorrhea were associated with higher concentrations of serum testosterone, a lower total follicular volume, and an effective response to menotropins at a lower serum FSH and a lower dose of menotropins per kilogram body weight. These data suggest that serum dehydroepiandrosterone sulfate may be a precursor for ovarian steroidogenesis.

Adrenal Glands↗
PubMed1985

Irradiation and prolactin effects on rat mammary carcinogenesis: intrasplenic pituitary and estrone capsule implants.

The implantation of silicone capsules that contained estrone and that were adjacent to grafts of anterior pituitary tissue in the spleens of adrenalectomized glucocorticoid-deficient inbred F344 rats resulted in high circulating prolactin (Prl) levels without the untoward effects of chronic hyperestrogenism or of grafts of Prl-secreting pituitary tumors. All peripheral serum estrone titers were below the titers in sera of proestrous untreated intact rats. Peripheral serum estrone and Prl levels were, however, a function of capsule surface area over the capsule sizes tested (12-74 mm2); the elevated Prl levels persisted for as long as 700 days. In adrenalectomized glucocorticoid-deficient female rats, both 5 Gy gamma-irradiation alone and intrasplenic pituitary-estrone implants alone induced mammary carcinomas; the combination of these treatments induced a greater incidence of first carcinomas and reduced first carcinoma latency. There were, however, no marked differences in tumor incidence or latency due to differences in estrone capsule size. Finally, ovariectomy reduced first carcinoma risk in irradiated, pituitary-estrone-implanted rats but did not change the time of maximum risk. Ovarian secretory activity thus persisted in such rats and ovarian hormones synergized with Prl in mammary carcinoma induction.

Adenofibroma↗
PubMed1985

Elevated serum relaxin levels in multiple pregnancy after menotropin treatment.

The serum relaxin and human chorionic gonadotropin (hCG) concentrations were determined in 17 spontaneous singleton pregnancies and four singleton pregnancies and five multiple gestations that followed treatment with menotropins. The geometric mean serum relaxin concentrations for the control and postmenotropins singleton pregnancies were similar (both 1.13 ng/mL), but the geometric mean serum relaxin concentration for multiple gestations that followed treatment with menotropins was significantly higher (2.56 ng/mL, P less than .01). A significant regression of serum relaxin on either days from the last menstrual period or serum hCG concentration was demonstrated. Covariance analysis supported the conclusion that multiple gestation produced a significant increase in serum relaxin concentration.

Chorionic Gonadotropin↗
PubMed1985

Pathophysiology of the ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome occurred after induction of ovulation with menotropins (follicle-stimulating hormone and luteinizing hormone) and implantation of an intrauterine pregnancy. Serial determinations of aldosterone, deoxycorticosterone, 17 beta-estradiol, progesterone, human chorionic gonadotropin, urinary and plasma electrolytes, and fluid balance were obtained. Plasma renin activity, aldosterone, deoxycorticosterone, and antidiuretic hormone rose markedly. Hydration for four days improved urinary output but also accelerated sodium and fluid retention. Subsequent restriction of salt and water stabilized the patient. Spontaneous abortion was followed by prompt diuresis without a change in therapy. Regression analysis of the authors' data, the clinical observations, and other data in the literature suggest that the ovarian hyperstimulation syndrome is produced by excessive secretion of an unknown hormone that regulates peritoneal fluid during the normal menstrual cycle, and that elevations of plasma renin, aldosterone, and antidiuretic hormone are secondary.

Adult↗