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Biomedical subjects

J S Winter

Publications and source records attributed to J S Winter.

At least 91 records · Page 5Linked to original sources

The relationships between serum concentrations of 17OH-progesterone and other serum and urinary steroids in patients with congenital adrenal hyperplasia.

Simultaneous determinations of serum concentrations of 17OH-progesterone, testosterone, androstenedione, and progesterone, and of urinary excretion of 17-ketosteroids and pregnanetriol have been performed at intervals in 31 patients with the C21-hydroxylase form of congenital adrenal hyperplasia. In prepubertal patients there were highly significant correlations between levels of 17OH-progesterone and those of testosterone, androstenedione, and progesterone, respectively. Similar correlations were observed in adolescent girls. In adolescent boys rising 17OH-progesterone levels were reflected by increasing levels of androstenedione and progesterone, but there was no change in serum testosterone concentrations. Levels of serum 17OH-progesterone below 200 ng/dl were uniformly associated with normal serum concentrations of testosterone, androstenedione, and progesterone, and normal urinary 17-ketosteroid and pregnanetriol excretion. In contrast, levels above 1000 ng/dl were accompanied by increased levels of the other steroids except in adolescent males; in this group the finding of unchanging serum testosterone concentrations in spite of rising 17OH-progesterone levels presumably indicates that testosterone of adrenal origin causes suppression of testicular testosterone production, either through a direct effect upon Leydig cells or via suppression of LH release.

17-Ketosteroids↗

Development of anti-hLH antibodies after therapy with posterior pituitary extract.

This report describes the appearance of high affinity antibodies to human LH in a girl who had been treated for diabetes insipidus with injections of pitressin tannate, plus occasional nasal insufflations of posterior pituitary powder. Immunological studies indicated that the antibody was a 7S IgG directed against the beta subunit of LH, which is not species-specific. The demonstration of immunoassayable LH in a commercially available pitressin preparation strongly suggests that this patient was immunized by bovine or porcine LH. Although studies of her urinary LH excretion and serum LH (by an interstitial cell bioassay system) suggest that at least some of her endogenous LH is not bound by the antibody, the possibility remains that this type of immunization may have important implications for the development and maintenance of normal adult pituitary-ovarian relationships.

Antibodies↗

Studies on human sexual development. VI. Concentrations of unconjugated dehydroepiandrosterone, estradiol, and estriol in amniotic fluid throughout gestation.

Concentrations of unconjugated dehydroepiandrosterone, estradiol, and estriol were measured in samples of amniotic fluid from uneventful pregnancies of 9-40 weeks conceptual age. There was no apparent influence of fetal sex upon the levels of these steroids. Dehydroepiandrosterone concentrations rose slightly from 9-20 weeks, and then showed little further change. Estradiol concentrations declined slightly from 9-20 weeks; after 32 weeks gestation, there was a 2-fold rise to term. Estriol levels rose in almost exponential fashion throughout gestation.

Amniotic Fluid↗

Maternal serum estrogen and progesterone concentrations preceding normal labor.

Simultaneous measurement of serum concentrations of estrone (E1), estradiol (E2), estriol (E3), and progesterone were carried out in multiple serial blood samples obtained during the last 3-10 weeks of pregnancy, labor, and the immediate postpartum period in 5 normal women. Estrogen and progesterone levels showed a small, but statistically significant diurnal variation during pregnancy. They did not change during labor; however, with the exception of E1 levels, all declined following delivery. Individual patterns preceding labor, derived from calculated moving mean values, showed no consistent decline in progesterone levels nor a surge in E1 and E2 concentrations whereas estriol levels showed a steady rise starting 14-28 days prior to the onset of labor. Whether this E3 elevation reflects fetal maturation and/or plays a role in the triggering mechanism of labor is unknow. Failure to detect changes in E1, E2, and progesterone levels in the maternal peripheral circulation does not preclude the possibility that alterations of metabolism of these hormones in the fetal or uterine compartments might be involved in the initiation of human labor.

Adult↗

Pituitary-ovarian relationships preceding the menopause. I. A cross-sectional study of serum follice-stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone levels.

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol, and progesterone concentrations were measured in 58 ovulating women in different age groups (20 to 29, 34 to 39, 40 to 44, and 45 to 50 years) at five- to seven-day intervals through a single menstrual cycle and in 18 postmenopausal women sampled weekly five to six times. The over-all hormone patterns were similar in four premenopausal groups. However, mean serum FSH levels increased with age and significantly higher concentrations were found in the 40 to 50 years group than in the 20 to 29 year group. Serum LH levels did not show a similar rise with age, although follicular LH levels in the oldest group were higher than in the 20 to 29 year group. Prolactin and estradiol concentrations did not change with age prior to the menopause, but luteal progesterone levels were lower in the three older premenopausal groups than in the 20 to 29 year group. Postmenopausal women showed elevated FSH and LH, decreased prolactin, and negligible estradiol and progesterone levels. There was an over-all significant linear correlation between prolactin and estradiol concentrations. It appears that the menopause is preceded by several years of rising gonadotropin, predominantly FSH, levels. During this period, ovarian estrogen production appears to be maintained and ovulation continues, but luteal progesterone levels decline. It is likely that these premenopausal alterations in pituitary-ovarian relationships reflect depletion of ovarian follicles.

Adult↗

Early diagnosis of salt-losing congenital adrenal hyperplasia in a newborn boy.

Assays of serum 17-hydroxyprogesterone concentration may be relied upon to establish a diagnosis of congenital adrenal hyperplasia within a few hours of birth. In a male infant the concentration of 17-hydroxyprogesterone was increased in cord serum and remained elevated until glucocorticoid therapy was started on the 5th day of life. Plasma renin activity was increased only slightly in the first few days, but a striking increase on day 5, along with a gradual increase in the serum potassium concentration, confirmed that the infant had the salt-losing form of congenital adrenal hyperplasia. It was not possible to demonstrate an increased concentration of 17-hydroxyprogesterone, in amniotic fluid obtained at 30 weeks' gestation, presumably because of interference in this assay by cross-reacting steroids. Studies of the mother's serum concentration of 17-hydroxyprogesterone and cortisol during delivery did not disclose any deviation from normal.

Adrenal Hyperplasia, Congenital↗

Studies on human sexual development. IV. Fetal pituitary and serum, and amniotic fluid concentrations of prolactin.

Prolactin concentrations were measured in 161 amniotic fluid specimens from 8-40 weeks fetal age and the levels compared with those observed in 45 fetal and neonatal cord sera and in 42 fetal pituitary specimens. Amniotic fluid prolactin levels rose steeply between 12-16 weeks gestation, and then declined to term; the calculated total amniotic fluid content of prolactin showed a similar pattern, but the peak was later, at about 26 weeks gestation. Amniotic fluid concentrations consistently exceeded fetal serum prolactin levels, even during the last trimester, when fetal serum and pituitary levels were highest. The data are compatible with a fetal origin for amniotic fluid prolactin, but only if one assumes that flux of prolactin out of amniotic fluid compartment is negligible, that the fetal kidney in mid-pregnancy clears prolactin at a rate virtually equal to the glomerular filtration rate, and the fetal pituitary shows secretion characteristics quite different from those of the adult gland.

Amniotic Fluid↗

Studies on human sexual development. V. Concentrations of testosterone, 17-hydroxyprogesterone and progesterone in human amniotic fluid throughout gestation.

Concentrations of unconjugated testosterone, 17-hydroxyprogesterone (170HP) and progesterone were measured by radioimmunoassay in amniotic fluid (AF) specimens from normal pregnancies of 9-40 weeks gestation. In two-thirds of samples from pregnancies with male fetuses. AF testosterone exceeded the upper limit found in female samples, with minimal overlap in the 12-18 week period of gestation. Although AF testosterone levels associated with male and female fetuses were both significantly lower toward term, the sex-difference persisted. Between 9-19 weeks gestation, fetal sex was also found to influence AF 170HP, a steroid thought to be predominantly of placental and fetal adrenal origin; in this case, female levels exceeded male. Awareness of the influence of sex and gestation upon AF concentrations of these steroids is an important prerequisite for their application to the prenatal diagnosis of endocrine disease (e.g., congenital adrenal hyperplasia). There was no sex difference in AF progesterone concentrations at 12-18 weeks gestation. The median progesterone concentration at 34-40 weeks was higher with female fetuses, but this difference may be related to a difference in gestational age between AF samples obtained from male and female fetuses.

Amniotic Fluid↗

Sex steroid production by the human fetus: its role in morphogenesis and control by gonadotropins.

Normal male genital differentiation requires fetal testicular secretion of both testosterone and the nonsteroidal müllerian-inhibitory factor. It appears that secretion of testosterone, at least during the critical period of differentiation, occurs in response to stimulation by CG, although pituitary LG may influence Leydig cell function in later fetal life. To date, there is no evidence to support a similar endocrine function for the fetal ovary in female genital differentiation. In both sexes normal fetal pituitary gonadotropin secretion appears to be required for maturation of the germ cells and related elements. The pattern of FSH and LH secretion in the fetus reflects gradual maturation of a functional hypothalamo-pituitary unit responsive to feedback inhibition by sex steroids. The higher levels of gonadotropins in female fetuses from from 12--20 weeks suggest either that this maturation occurs earlier in males than in females, or, more probably, that feedback recognition of androgens is established before gestation reflects development of an estrogen-mediated feedback mechanism, and in addition the possible influence that hormones, such as prolactin or placental estradiol, may have on testicular steroidogenesis.

Androgens↗

A report on missile injuries in Cyprus 1974.

This paper details the experiences of the Princess Mary's Royal Air Force Hospital, Akrotiri (TPMH), during the last 6 months of 1974. TPMH was at that time a small hospital (120 beds) with a clinical staff of 17 situated in the south of Cyprus (fig. 1). The series comprises 71 patients injured by bullets, shrapnel, bomb-blasts or mines, drawn from British personnel, United Nations Forces and the local Cypriot military and civilian population, resulting from the coup d'état of 15 July 1974 and the subsequent Turkish invasion and air attacks. The casualties were often severely wounded beyound the capabilities of the local hospitals. They were mostly admitted during a 2-week period, but many required multiple operations extending over the next 3 or 4 months, and altogether 119 operations were carried out on 41 patients at TPMH. The organization of the limited resources of the medical, nursing and supporting staff is outlined. The correct treatment of missile wounds is emphasized. Resuscitation, wound excision, splintage and delayed suture or grafting are essential. Minimal morbidity and mortality are gained by a practised approach to the compounded results of violence.

Adult↗

The application of a serum 17OH-progesterone radioimmunoassay to the diagnosis and management of congenital adrenal hyperplasia.

Serum concentrations of 17OH-progesterone were studied serially over 24 hours in 13 treated and untreated patients with the C21 hydroxylase form of congenital adrenal hyperplasia. The results were correlated with measurements of plasma renin activity, serum electrolytes, and urinary 17-ketosteroids and pregnanetriol. In 500 healthy subjects from birth to adult life, serum 17OH-pregesterone levels ranged from 5 to 315 ng/dl. In untreated CAH, serum 17OH-progesterone was markedly elevated (2,000 to 80,000 ng/dl). Treatment with cortisol (20 to 30 mg/m2/day in 3 doses) resulted in normal serum 17OH-progesterone levels in both non-salt-losing and salt-losing patients receiving adequate mineralocorticoid. Even slightly inadequate mineralocorticoid therapy (shown by high plasma renin activity with normal serum electrolytes) was associated with elevated 17OH-progesterone (to 65,000 ng/dl) in spite of usually effective doses of cortisol. Some patients showed isolated 17OH-progesterone elevations (usually early morning), a situation which requires only revision of the cortisol dosage schedule without an increase in total dosage. The data confirm the value of 17OH-progesterone assays in both the diagnosis and management of CAH. Taken together with determinations of plasma renin activity, serum 17OH-progesterone assays can permit more exact control of CAH without excessive doses of glucocorticoid.

17-Ketosteroids↗

Reproductive endocrinology of female chimpanzees: a suitable model of humans.

Similarities between reproductive processes in humans and chimpanzees have led to speculation that the chimpanzee might be an excellent reproductive-endocrine model of humans. Data comparing patterns and concentrations of serum gonadotropins, prolactin, and sex steroids in female humans, chimpanzees, and rhesus monkeys sustain this concept. The striking evidence that levels of estrone, estradiol, estriol, progesterone, and chorionic gonadotropin are similar during human and chimpanzee pregnancy support the contention that chimpanzees, like humans but unlike rhesus monkeys, have a definitive fetoplacental unit. Likewise, during normal menstrual cycles serum patterns of LH, FSH, progesterone, and estradiol are similar in women and chimpanzees, but differ in rhesus monkeys. Thus by using the chimpanzee it may be possible to accurately assess the safety for human use of compounds that might affect reproductive-endocrine processes without direct exposure to humans.

Animals↗

Studies on human sexual development. III. Fetal pituitary and serum, and amniotic fluid concentrations of LH, CG, and FSH.

Fetal sera (9-20 weeks fetal age, n = 80) and pituitary glands (9.5-20 weeks, n = 36) obtained from hysterotomy specimens, and amniotic fluids (amniocentesis; 8-40 weeks, n = 123) were assayed for FSH, LH (betaLH assay) and CG (betaCG assay). Results are expressed as mass of pure hormone. Prior to 12 weeks fetal age, pituitary, serum and amniotic fluid concentrations of LH and FSH were low or unmeasurable. In contrast, levels of CG in serum and in amniotic fluid were clearly measurable prior to 12 weeks. There was a definite CG peak at 11-14 weeks with levels up to 550 ng/ml in serum and 7400 ng/ml in amniotic fluid. Although LH levels began to rise at 12 weeks, when CG levels started to decline, serum levels of LH from 14-20 weeks in males (2-13 ng/ml) were still lower than the majority of CG levels at this time (6-115 ng/ml). These observations suggest that CG is the primary stimulus to the fetal Leydig cell which results in testosterone secretion (peak 11-17 weeks) and masculine differentiation of the genital tract. Significantly lower concentrations of both FSH and LH were observed in pituitary, serum and amniotic fluid between 12-20 weeks fetal age in males compared to females. This may be a result of feedback inhibition by the higher concentrations of testosterone in males at this time. Amniotic fluid FSH and LH concentrations correlated with their respective serum and pituitary values (P less than 0.01) indicating that amniotic fluid may provide a convenient index of fetal serum concentrations.

Amniotic Fluid↗

Pituitary gonadotropin function during human pregnancy: serum FSH and LH levels before and after LHRH administration.

Pituitary gonadotropin reserve was evaluated in 8 normal pregnant women (13-35 weeks gestation) by measuring serum concentrations of FSH and LH (betaLH assay) before and after an IV bolus of 100 mug LHRH. Basal levels of FSH and LH were low or undetectable. LHRH administration failed to stimulate FSH release but did result in a small short-lived rise in LH levels. These findings provide further evidence that pituitary gonadotropin synthesis and release are inhibited during pregnancy.

Female↗

Pituitary-gonadal relations in infancy: 2. Patterns of serum gonadal steroid concentrations in man from birth to two years of age.

Testosterone, estradiol, 170H-progesterone, and androstenedione (except in cord samples) concentrations were determined in cord sera (30 male and 14 female) and in peripheral sera from infants (121 male and 110 female), age 1 day to 2 years. Male and female cord serum levels of these steroids were not significantly different. In both sexes levels during the first week were lower than those in cord sera. In male infants serum testosterone and 170H-progesterone levels rose sharply in the second week of life, reached a peak at 1-2 months, and then declined to the range seen in later childhood by 6 months of age; male serum androstenedione and estradiol concentrations were higher during the first 2 months of life, but no distinct pattern of rise and fall was seen. In girls serum testosterone levels fell in the first week to the range seen throughout childhood; serum concentration of estradiol, androstenedione, and 17OH-progesterone in girls were markedly variable, with many values above the childhood range being seen, particularly in the first 6 months. These data provide further evidence of active Leydig cell function in male infants. They suggest that there is also ovarian secretion of sex steroids in some female infants in response to the elevated FSH and LH levels which are seen at this time.

Adolescent↗

Endocrine effects of vasectomy in man.

Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and free testosterone index (FTI) were measured serially in 11 fertile men, ages 25 to 40, 4 weeks before to 40 weeks after elective vasectomy. During the 1st week postvasectomy there was a significant fall in FSH levels (P less than 0.001) and FTI (P less than 0.05), with recovery by 2 weeks. This acute response may be due to general surgical stress. Thereafter, the over-all mean FSH level was significantly (P less than 0.05) below the prevasectomy level; over-all levels of LH, T, and FTI did not change. We speculate that this decline in mean FSH levels is compatible with the existence of an as yet unidentified T-independent testicular factor influencing FSH production.

Adult↗