Showing papers in "The Journal of Clinical Endocrinology and Metabolism in 1976"

The Menopausal Transition: Analysis of LH, FSH, Estradiol, and Progesterone Concentrations During Menstrual Cycles of Older Women

Abstract: Studies of menstrual cycle length in large populations demonstrated that there is a striking increase in the variability of intermenstrual intervals just before menopause. The changes in serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) during menstrual cycles in a group of perimenopausal women were compared with the findings in young normal women. In 8 women, 46-56 years old with regular cycles, cycle length was shorter and the mean E2 concentration was lower than in younger women. There was a striking increase in FSH concentration throughout the cycle while LH remained in the normal range. In 2 women, 14 cycles of variable length were studied during 2 years of the menopausal transition. In some instances, hormonal changes associated with follicular maturation and corpus luteum function occurred in the presence of high, menopausal levels of LH and FSH with a diminished secretion of E2 and P. In others vaginal bleeding occurred during a fall in serum E2 with no associated rise in P. Cycles of variable length during the menopausal transition may be due either to irregular maturation of residual follicles with diminished responsiveness to gonadotropin stimulation, or to anovulatory vaginal bleeding that may follow estrogen withdrawal without evidence of corpus luteum function. The observation of elevated FSH concentrations and normal LH levels in perimenopausal women emphasizes the complexity of the hypothalamic-pituitary-ovarian regulatory system and suggests that LH and FSH are modulated independently at the level of the pituitary.

Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests.

Abstract: Insulin secretion and glucose disappearance rate were measured in 66 subjects with a wide range of fasting plasma glucose levels. The acute insulin response was present in subjects with fasting glucose levels below 115 mg/dl but was absent above this level. The glucose disappearance rate related to the relative acute insulin response in subjects with fasting glucose below 115 mg/dl and to total insulin response when fasting glucose levels were above 115 mg/dl. A calculated glucose disappearance rate of 1.06 per cent per minute was found when the acute isulin response was zero. All subjects with fasting glucose levels greater than 115 mg/dl had glucose disappearance rates greater than 1.06. These studies support 1) epidemiological data indicating 115 mg/dl as an upper limit of normal for fasting plasma glucose levels and 1.0 per cent per minute as a lower limit of normal for the glucose disappearance rate, and 2) evidence for an important role for the acute insulin response in the determination of glucose disappearance rates during intravenous glucose tolerance tests.

The Hormonal Activity of the Postmenopausal Ovary

Abstract: The origin of plasma sex hormones in postmenopausal women was studied by determining plasma levels under basal conditions, after ACTH stimulation, and after dexamethasone suppression, as well as after hCG stimulation. Values obtained in postmenopausal women were compared with values observed during the follicular phase of the cycle in young women on the one hand, and with values in ovariectomized women of postmenopausal age on the other hand. All sex steroid levels studied with the exception of estrone, were significantly lower in postmenopausal women than in young women during the early follicular phase of the cycle. In ovariectomized women only androgen levels (testosterone, androstenedione, dihydrotestosterone, and to a lesser extent dehydroepiandrosterone,) were lower than in normal postmenopausal women, estrogen, 17 hydroxyprogesterone, and progesterone levels being similar. ACTH increased all plasma steroid levels except estradiol, whereas after dexamethasone, all sex hormone levels were significantly decreased. hCG stimulation finally caused an increase of borderline statistical significance in testosterone, dehydroepiandrosterone, and 17-hydroxyprogesterone levels. We have concluded from this study that the adrenal cortex is almost the exclusive source of plasma estradiol, estrone, progesterone, and 17OH progesterone and the most important source of plasma dehydroepiandrosterone; that the postmenopausal ovary appears to be responsible for about 50% of plasma testosterone and 30% of androstenedione levels; and that hCG stimulation with 5000 IU daily for 3 days, hardly influences steroid secretion by postmenopausal ovaries.

Pituitary-Gonadal Relations in Infancy: 2. Patterns of Serum Gonadal Steroid Concentrations in Man from Birth to Two Years of Age

Abstract: Testosterone, estradiol, 17OH-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 17OH-progesterone levels rose sharply in die 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 concentrations of estradiol, androstenedione, and 17OH-progesterone in girls were markedly variable, with many values above the childhoo...

The effect of glucocorticoid administration on human pituitary secretion of thyrotropin and prolactin.

Abstract: In order to determine the mechanism by which glucocorticosteroids decrease the serum concentration of thyrotropin (TSH), we studied eight normal subjects before and after they received 16 mg of dexamethasone daily for 2½ days. Serum levels of TSH and prolactin (PRL) were measured in the basal state and in response to the intravenous administration of 200 μg thyrotropinreleasing hormone (TRH); T4, free T4 (fT4), T3, and free T3 (fT3) were measured before TRH injection. Metabolic clearance rates of TSH corrected for body surface area (MCR-TSH/m2) were determined by the method of constant infusion to equilibrium; the production rates of TSH (PR-TSH/m2) were calculated. Dexamethasone produced a decrease in basal TSH from 2.2 to 0.8 μU/ml (P < 0.02), a statistically insignificant elevation in MCR-TSH/m2 from 25.8 to 34.1 ml/min/m2, and a decrease in PRTSH/m2 from 79 to 30 mU/day/m2 (P < 0.01). Peak TSH response to TRH decreased from 16.4 to 5.8 μU/ml (P < 0.005), as did TSH reserve from 1.58 to 0.54 m...

The Interaction of Blood Osmolality and Blood Volume in Regulating Plasma Vasopressin in Man

Abstract: The effect of blood volume on the osmotic control of the antidiuretic hormone, arginine vasopressin (AVP), has been studied in 18 healthy young adults. Changes in blood osmolality and/or volume were produced by each of 3 procedures--fluid deprivation, orthostasis, and hypertonic saline infusion--and the resultant changes in plasma AVP were measured by radioimmunoassay and expressed as a function of the simultaneous level of plasma osmolality. When the subjects were hydropenic and recumbent, a highly significant correlation between plasma AVP and osmolality was observed that was described by the regression equation y = 0.35 (x -281.0) where y represents the plasma AVP concentration in pg/ml and x the plasma osmolality in mosmol/kg. When these same hydropenic subjects were studied in the upright position, a maneuver that reduces intrathoracic blood volume, plasma AVP and osmolality still showed a significant correlation, but the regression equation describing this relation, y = 0.31 (x -277.8), occupied a position significantly to the left of that found during recumbency. Conversely, when the same subjects were studied during infusion of hypertonic saline, a procedure that increases blood volume, plasma AVP and osmolality again correlated significantly but the regression equation describing this relation, y = 0.32 (x -282), now occupied a position significantly to the right of that obtained during recumbent and hydropenic conditions. These results indicate that moderate increases or decreases in blood volume do influence the osmoregulation of AVP in man, but the effects are relatively small and limited to adjustments in the set of the receptor toward higher or lower levels of osmolality.

Cortisol-induced suppression of plasma testosterone in normal adult males.

Abstract: The response of plasma testosterone, LH and FSH to oral administration of cortisol or dexamethasone was studied for 26 h in 6 groups of 12 normal adult males. Twenty-four hour treatment with cortisol (60 mg at 1000 h, followed by 30 mg at 2 h intervals) or with dexamethasone (6 mg at 1000 h, followed by 3 mg at 6 h intervals) was without effect on testosterone during the day but suppressed the nocturnal rise completely. LH and FSH did not decrease at any time during the day and showed a highly significant increase during the second part of the night. Short-term treatment (1000–1600 h, 1600–2200 h or 2400 h–0800 h) with cortisol was less effective in suppressing the nocturnal rise in testosterone. It was concluded that administration of cortisol leading to plasma levels as seen under treatment with ACTH suppresses testosterone by abolishing or flattening the nocturnal rise. This effect was not mediated by changes in LH or FSH. Our data suggest that the ACTH-induced suppression of testosterone is d...

Effects of Dopamine Infusion on Pituitary Hormone Secretion in Humans

Abstract: Dopamine, infused at a rate of 4 mug/kg/min for 3-4 h unaccompanied by any significant changes in cardiovascular dynamics, induced a prompt and sustained suppression of circulating prolactin (PRL) levels in normal men and women as well as in patients with hyperprolactinemia At the discontinuation of the infusion, there was a marked rebound in PRL levels in normal subjects and a rapid return to basal levels in hyperprolactinemic patients Dopamine infusion also induced a significant fall in LH levels in the normal subjects with a marked rebound in LH levels following the infusion No significant changes in GH, TSH, and FSH levels were observed These data indicate that in man a dopaminergic mechanism ixists in the regulation of PRL secretion and that dopamine also exerts an inhibitory effect of LH release

Effect of caloric restriction and dietary composition on serum t3 and reverse t3 in man

Abstract: To evaluate the effect of caloric restriction and dietary composition on circulating T3 and rT3 obese subjects were studied after 7-18 days of total fasting and while on randomized hypocaloric diets (800 kcal) in which carbohydrate content was varied to provide from 0 to 100% calories. As anticipated, total fasting resulted in a 53% reduction in serum T3 in association with reciprocal 58% increase in rT3. Subjects receiving the no-carbohydrate hypocaloric diets for two weeks demonstrated a similar 47% decline in serum T3 but there was no significant change in rT3 with time. In contrast, the same subjects receiving isocaloric diets containing at least 50 g of carbohydrate showed no significant changes in either T3 or rT3 concentration. The decline in serum T3 during the no-carbohydrate diet correlated significantly with blood glucose and ketones but there was no correlation with insulin or glucagon. We conclude that dietary carbohydrate is an important regulatory factor in T3 production in man. In contrast, rT3 concentration is not significantly affected by changes in dietary carbohydrate. Our data suggest that the rise in serum rT3 during starvation may be related to more severe caloric restriction than that caused by the 800 kcal diet.

Hyperprolactinemic anovulatory syndrome.

Abstract: The functional status of the hypothalamo-pituitary-gonadal axis was investigated in 127 women with anovulatory disease. Radioimmunoassayable circulating LH, FSH, and prolactin concentrations were measured. An attempt was made to localize the functional lesion by utilizing the following criteria: 1. Hypothalamic function: a) clomiphene test based upon hormonal parameters; b) recording of the pulsatile LH fluctuation (spiking) and of basal FSH. 2. Pituitary function: determination of the gonadotropin reserve by means of a standardized LRH test. 3. Ovarian function: a) measurement of plasma E2 and progesterone levels by RIA; b) gestagen bleeding test. All patients had amenorrhea of up to 14 years duration. A total of 17 hyperprolactinemic patients (13.4%) was found. Eight of these patients never experienced galactorrhea, in 7 only transient galactorrhea was reported, and in 2 cases galactorrhea persisted. All hyperprolactinemic patients were found to be clomiphene non-responders as well as nonspikers. The pi...

Impaired Release of Parathyroid Hormone in Magnesium Deficiency

Abstract: Parathyroid hormone release and endorgan responsiveness to parathyroid extract (PTE) were evaluated in a 25-year-old woman with magnesium deficiency associated with hypocalcemia and inappropriately low levels of serum immunoreactive parathyroid hormone (iPTH). End-organ responsiveness to PTE was demonstrated by increases in serum calcium and in urinary phosphorus, cyclic AMP, and hydroxyproline. When the serum calcium was increased from a baseline of 6.9 mg/100 ml to levels of 8.0 mg/100 ml and higher by calcium infusion, the serum iPTH decreased from the low normal range to below the limits of detectability. The intravenous administration of 3 mg/kg of body weight of magnesium led to an abrupt and striking increase in circulating iPTH with a 2-fold increase in one minute, a 6-fold increase in two minutes, and an 8-fold increase in five minutes. The very rapid increase in serum iPTH produced by magnesium infusion in this study suggests an effect of magnesium on hormone secretion rather than an ef...

Human Thyroid Adenyl Cyclase-Stimulating Activity in Immunoglobulin G of Patients with Graves' Disease

Abstract: We have studied the characteristics of the stimulation of adenyl cyclase (AC) activity in human thyroid plasma membranes by thyroidstimulating hormone (TSH) and by immunoglobulin G (IgG) from the sera of patients with Graves' disease. AC activity was measured as adenosine 3′,5′-cyclic monophosphate (cAMP) generated by membranes in a 10 minute incubation. IgG from two patients with Graves' disease possessed particularly potent human thyroid AC-stimulating activity; the dose-response curves with these IgGs were essentially parallel to those obtained with TSH. As little as 30 μg of the IgG of one patient with Graves' disease or 8 μU of TSH caused significant AC stimulation. A Lineweaver-Burk plot of the data suggested similarity in the site of action of both TSH and human thyroid adenyl cyclase stimulator (HTACS) in Graves' IgG. Submaximal doses of HTACS and TSH had additive effects on AC stimulation, but a large dose of a Graves' IgG with potent AC stimulating activity did not enhance AC stimulation by a ma...

Studies on Human Sexual Development. III. Fetal Pituitary and Serum, and Amniotic Fluid Concentrations of LH, CG, and FSH

Abstract: 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 (βLH assay) and CG (βCG 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.

Diagnosis and Nomenclature of the Disorders of the Terminal Portion of the Aldosterone Biosynthetic Pathway

Abstract: The abnormal steroid pattern in an inborn error in aldosterone biosynthesis consists of overproduction of glomerulosa zone 18-hydroxycorticosterone relative to aldosterone. The normal values for the excretory ratio of the major umiary metabolites of these two steroids are presented to provide a basis for the diagnosis of abnormalities in their ratio. The production of glomerulosa zone 18-hydroxycorticosterone relative to aldosterone is remarkably constant over a large range of absolute values, except in the disorder involving the terminal portion of the aldosterone biosynthetic pathway for which the term corticosterone methyl oxidase defect, Type 2, is suggested.

Plasma adrenal and gonadal sex steroids in human pubertal development.

Abstract: Plasma free dehydroepiandrosterone (DHA), androstenedione (delta), testosterone (T), dihydrotestosterone (DHT), estrone (E1), and estradiol (E2) were measured by radioimmunoassay in 55 boys and 54 girls 3.5 to 16.3 years of age. Plasma DHA increased significantly between 6 and 8 years of age in girls and between 8 and 10 years of age in boys. A further significant increase was noted between 10 and 12 years of age in both sexes. Delta rose significantly between 8 and 10 years of age in girls and between 10 and 12 years in boys. In contrast, no significant increase in T, DHT, or E1, was noted prior to 12 years of age in both sexes. However, E2 showed a significant increase between 10 and 12 years of age in girls. This early rise in the course of pubertal development of the two sex steroids predominantly of adrenal origin, DHA and delta, and its occurence 1 to 2 years earlier in girls than in boys, as does puberty itself, suggest a possible role for these steroids in the mechanisms involved in triggering the hypothalamic-pituitary-gonadal axis at puberty.

Serum Androgens in Normal Prepubertal and Pubertal Children and in Children with Precocious Adrenarche

Abstract: Serum androgens testosterone (T), testosterone-like-substances (TLS), delta4-androstenedione (delta4), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) were measured in 85 normal girls and 101 normal boys grouped according to pubic hair development in Tanner stages I to IV/V. The pattern of change with puberty differed for each androgen. In boys T and TLS rose with the onset of puberty but showed a more abrupt rise later in puberty. DHT also was higher in boys in late puberty but did not demonstrate a steep rise. The other androgens did not show a sex difference at any stage of puberty. While delta4 steroids did not show an increase in the years before onset of puberty, DHEA was significantly higher in prepubertal children over 7 years than in those under 7 years (mean +/- SD 166 +/- 110 vs. 31 +/- 25, P less than 0.005). The most rapid increase of DHEA concentrations was observed with the appearance of pubic hair (Stage II) in boys and girls. This contrasted with the more gradual rise of delta4 in both sexes. The oldest boys and girls (Tanner stages IV/V) had mean concentrations of all androgens in the adult range except for DHT. Twenty-two girls with precocious adrenarche (PA) aged 3-8 years had mean concentrations of T, DHT, delta4 and DHEA that were significantly higher (P less than 0.05) than in prepubertal children, but similar to those of girls in stage II and significantly lower (P less than 0.02) than in late pubertal girls (stage IV/V). Longitudinal studies in 12 of the girls indicated fluctuation of androgen concentrations, especially DHEA, but in general no increase during the years of followup. Precocious adrenarche appears to be a non-progressive disorder associated with an advanced maturation of adrenal androgen to an early pubertal stage. A rise in all androgens measured was correlated with the development of sexual hair.

Nocturnal elevation of plasma melatonin and urinary 5-hydroxyindoleacetic acid in young men: attempts at modification by brief changes in environmental lighting and sleep and by autonomic drugs.

Abstract: In order to determine whether the human pattern of circulating melatonin resembles that previously described in lower animals, men 19-32 years old were exposed to a light-dark cycle with 14 hours of light per day (L:D 14:10). In whites and blacks, nocturnal (dark phase, sleeping) melatonin levels were almost always elevated to 0.05-0.1 ng/ml plasma compared with lower or undetectable levels during the day, measured by the tadpole bioassay. Thin-layer migration of bioactive material was identical to that for melatonin standard. A rhythm with nocturnal elevation of urinary 5-hydroxyindoleacetic acid (5-HIAA) was observed. Nocturnal (sleep phase) rise in blood melatonin (but not urinary 5-HIAA) continued during 21/2 day-night cycle lengths after the onset of constant light. Though the dark phase plasma melatonin rise was less marked after reversal of the sleep-wake cycle (no change in the light cycle), dark phase rise in urinary 5-HIAA continued. Though marked cardiovascular and other effects were produced by intravenous isoproterenol or scopolamine, no definite effect on melatonin levels was observed after either drug during the light phase in waking subjects.

Changes of circulating thyroxine, triiodothyronine and reverse triiodothyronine after radiographic contrast agents.

Abstract: Thyroid function was studied for 42 days in 58 patients, 28 of whome had euthyroid goiter, after urography (diatrizoic acid), cholangiography (ioglycamic acid), and cholecystography (Naiopanoate) After urography and cholangiography short-lived increases of the serum thyroxine occurred in a few patients, but the mean thyroxine and triiodothyronine concentration did not change By contrast, 7 days after oral cholecystography serum thyroxine had risen consistently by 22% with a concomittant rise of the free thyroxine, while triiodothyronine declined by 15% The thyroxine metabolite 3,3',5'-triiodo-1-thyronine (reverse T3) rose by 50% and serum thyrotropin concentration doubled After 42 days thryoxine and triiodothyronine had returned to baseline, and none of the 58 patients developed clinical hyperthyroidism In patients with severe myxoedema kept on a constant replacement dose with 1-thyroxine NA-iopanoate produced similar changes with the exception of the rise of the serum thyroxine The primary event after Na-iopanoate seems to be a fall of the serum triiodothyronine, which in turn augments thyrotropin and indirectly thyroxine secretion the marked and sometimes sustained rose of serum thyroxine after cholecystography may lead to the erroneous diagnosis of hyperthyroidism

Dietary phosphate deprivation in women and men: effects on mineral and acid balances, parathyroid hormone and the metabolism of 25-OH-vitamin D.

Abstract: We evaluated the effects of dietary PO4 restriction on 25-OH-Vitamin D3 metabolism, serum iPTH levels, and mineral balances in healthy women and men. PO4 balances were progressively negative because of fecal losses without sex difference. Turnover of the plasma 25-OH-D pool was increased from 5.8 ± 0.4 to 12 ± 1.2 nmol/day; P < 0.001, despite a fall in serum iPTH of −1.1 ± 0.3 μlEq/ml; P < 0.01. In both sexes, net intestinal calcium and magnesium absorption increased in proportion to a more rapid turnover of the plasma 25-OH-D pool, implying increased renal 1, 25-(OH)2-D3 production. By contrast, there was a striking sex difference in the response of serum PC4, to dietary PO4 deprivation; the levels falling progressively in women, but remaining at control levels in men. Women demonstrated progressive hypercalciuria and negative Ca balances while in men the increments in intestinal Ca absorption were approximately matched by the increments in urinary Ca excretion so that Ca balances were not different from...

Acute and chronic estrogen effects upon serum somatomedin activity, growth hormone, and prolactin in man.

Abstract: Estrogen (E) reduces bioassayable GH-dependent serum somatomedin (SM) activity in acromegalics without affecting plasma growth hormone (GH) levels and inhibits the rise of SM activity normally produced by GH administration in GH-deficient subjects. We have now investigated the effect of E administration on serum SM activity and on plasma GH and prolactin (PRL) in 6 adult male subjects without pituitary pathology. Chronic E administration (ethinyl estradiol 0.5 mg/day for 7 to 70 days) reduced serum SM activity by 40 to 62% in each of 4 subjects (P < 0.02 to <0.001). In 3 of the subjects, basal GH levels increased by 75 to 300% (P < 0.05 to <0.001) and basal PRL levels increased by 90 to 200% (P < 0.01 to <0.001). While iv administration of normal saline did not significantly affect either SM or GH, iv administration of E (bolus injection of 25 mg conjugated estrogens, USP) to 5 subjects resulted in: a) a 46 to 80% decrease in serum SM activity in all subjects, proceeding with an apparent half-lif...

Human serum melatonin changes during the menstrual cycle.

Abstract: Serum melatonin concentration in early morning during the menstrual cycle, studied in five healthy women, showed that melatonin was elevated at the time of menstrual bleeding and had its nadir at the time of the menstrual cycling in humans.

The Functional Changes of the Pituitary Gonadotrophs During the Menstrual Cycle

Abstract: Submaximal doses of LRF, administered over a period of several hours, either by repeated pulses (10 μg at 2 h intervals × 5) or by constant infusion (02 μg/min × 4 h), have permitted the assessment of changes in the releasable gonadotropin during the menstrual cycle Quantitations in the acute releasable and ultimately releasable gonadotropins were made which represent, respectively, the sensitivity and reserve of the gonadotrophs The functional expression of these two components of gonadotropin release exhibited profound changes during the menstrual cycle and were in synchrony with the cyclicity of ovarian steroid levels; during the early follicular phase, both sensitivity and reserve were at a minimum, but with increasing levels of E2, a preferential increase in reserve over sensitivity (P < 0005) was found Although both sensitivity and reserve increased dramatically near the midcycle, the relative change in these two components was reversed from the late follicular phase to the midcycle su

In vitro bioassay of LH in human serum: the rat interstitial cell testosterone (RICT) assay.

Abstract: A sensitive bioassay for serum LH and hCG has been developed by utilization of the testosterone response of collagenase-dispersed rat Leydig cells to gonadotropic stimulation in vitro. Testosterone production by dispersed interstitial cells is stimulated by human, ovine, bovine, porcine, rat and rabbit LH, and by hCG and pregnant mare serum gonadotropin. The rat testis interstitial cell assay gives parallel dose-response curves for all steroidogenic gonadotropins tested, and thus permits cross-species comparison of the intrinsic biological activities of native and modified gonadotropins. The sensitivity of the rat interstitial cell bioassay is equal to or higher than that of radioimmunoassay, with detection limits of 50 muU for hMG and 20 muU for hCG. The optimum conditions for bioassay of serum gonadotropins were provided by incubation of dispersed interstitial cells in the presence of 1-methyl 3-isobutyl xanthine with the addition of gonadotropin-free serum or 5% BSA to ensure a constant proportion of serum protein in all assay samples and standards. Assays performed under these conditions gave parallel dose-response curves and identical maximum responses to both standards and serum samples containing endogenous LH or hCG. All responses to human gonadotropin standards and serum samples in the bioassay were abolished by incubation in the presence of antisera to LH or hCG. This sensitive and specific method permits bioassay of basal levels of LH in male and female serum, and of the higher gonadotropin levels in postmenopausal and pregnant subjects after appropriate dilution of the serum samples. For normal men and women, serum samples of 25-100 mul are employed, while volumes of 1-20 mul are adequate for assay of LH in postmenopausal or hypogonadal subjects. Serum LH values in hypopituitary and oral contraceptive-treated subjects were usually undetectable, while LH levels in normal subjects were always measurable with good precision. The within-assay coefficient of variation for measurement of a normal male plasma pool (30 mU/ml) was +/- 10%, and the between-assay variation was +/- 15%. The precision of the assay (lambda) was 0.035 +/- 0.015 (n = 72). In 42 normal females, the bio: immuno (B:I) ratio for serum LH was 1.20 +/- 0.40 (SD), and no consistent change in ratio was observed throughout the menstrual cycle. By contrast, significantly higher B:I ratios were observed in normal males (2.5 +/- 0.4), postmenopausal females (2.6 +/- 0.6) and patients with Turner's syndrome (2.6 +/- 0.6). These findings suggest that the LH circulating in normal female plasma is similar in biological and immunological activity to hMG, whereas the LH present in normal male plasma and in states of increased gonadotropin secretion has a relatively higher biological activity. The rat interstitial cell bioassay provides for the first time a practical and precise assay for measurement of the biologically active LH levels in serum of normal biologically active LH levels in serum of normal human subjects.

Unconjugated dehydroepiandrosterone plasma levels in normal subjects from birth to adolescence in human: the use of a sensitive radioimmunoassay.

Abstract: A specific and sensitive radioimmunoassay for measuring unconjugated plasma dehydroepiandrosterone(DHA) has been developed and the results expressed in ng/100 ml Mean values ±1 SD were in mixed cord blood 5933 ± 1865 in 21 females and 7127 ± 1909 in 18 males During the first day of life the peripheral plasma concentration of DHA was 9176 ± 3178 in 22 female and 92265 ± 290 in 17 male neonates During the first month of age, DHA levels decreased significantly and then more progressively throughout the first year of life Mean levels observed between the first and 6th month of life were 1471 ±536 in 15 girls and 1516 ± 627 in 28 boys Between 6 and 12 months of age mean DHA levels were 909 ± 433 and 6814 ± 309 in 11 girls and 24 boys, respectively In 250 normal children, plasma DHA levels were very low between 1 to 6 years of age, but rising progressively thereafter without any sex difference long before any clinical sign of puberty A circadian rhythm parallel to that of cortisol was obse

Body Weight and the Pituitary Response to Hypothalamic Releasing Hormones in Patients with Anorexia Nervosa

Abstract: Fifteen women with anorexia nervosa were studied before and after weight gain. Basal plasma thyroid stimulating hormone (TSH) and prolactin (PRL), and the responses of both these hormones to thyrotropin releasing hormone (TRH), were normal. Basal plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) were low in patients who were emaciated, and their responses to gonadotropin releasing hormone (GnRH) were impaired. Both basal and stimulated levels of LH and FSH rose with weight gain, with a linear correlation between gonadotropin levels and body weight expressed as a percentage of standard. The FSH response became greater than normal in patients who had regained weight to more than 70% of standard, while the LH response to GnRH was exaggerated in those who had regained weight to more than 80%. Basal plasma estradiol (E2) levels were low at first, but returned to within the normal range in patients over 80% of standard. Menstruation resumed in some patients after they had regained weight. The relationship between body weight and gonadotropin levels appears to be an important feature of the menstrual disturbance in anorexia nervosa. The restoration of a normal body weight is a prerequisite for the resumption of menstruation in this condition, but other as yet unidentified factors may also be involved.

Catecholamine Metabolism in Thyroid Disease. II. Norepinephrine Secretion Rate in Hyperthyroidism and Hypothyroidism

Abstract: We have measured the secretion rate of epinephrine in 6 euthyroid, 6 hyperthyroid, and 6 hypothyroid subjects infused at a constant rate for a one hour period with tritiated epinephrine (.01 muc/kg/min) (New England Nuclear Inc.). Plasma and urinary levels of epinephrine were measured by modifying the fluorometric method of Anton and Sayre. Plasma levels of epinephrine were 3.0 +/- 3.0 ng/100 ml (mean +/- SD) in normal subjects, compared to 4.4 +/- 3.5 ng/100 ml (mean +/- SD) in hyperthyroid subjects. In urine, epinephrine values ranged from 1.3 mug/day to 6.1 mug/day in normal subjects. Mean value observed in hyperthyroidism was 4.9 +/- 2.6 mug/day and 3.8 +/- 1.0 mu/day in hypothyroidism. Plasma secretion rates averaged 48 +/- 27 mug/kg/day in normal subjects, compared to 54 +/- 18 mu/kg/day in hyperthyroidism and 43 +/- 20 mug/kg/day in hypothyroidism. Likewise, the mean urinary secretion rate was 55 +/- 27 mug/kg/day in normal subjects compared to 60 +/- 22 mug/kg/day in hyperthyroidism and 50 +/- 28 mug/kg/day in hypothyroidism. There is no statistical difference between the values found in the three groups of subjects (plasma and urine). Therefore, these results would indicate that the signs and symptoms encountered in hyperthyroidism are not secondary to a high secretion rate of epinephrine.

Serum 17β-Estradiol and Estrone Levels in Postmenopausal Women With and Without Endometrial Cancer

Abstract: Serum 17 beta-estradiol (E2) and estrone (E1) levels were measured before and 6-8 weeks after ovariectomy in 16 postmenopausal women with endometrial cancer, and in 10 postmenopausal women with normal endometrium (preovariectomy only). For E2, no significant difference in the mean baseline (+/-SE) level was found between the tumor (13.5 +/- 1.1 pg/ml) and non-tumor patients (11.7 +/- 1.4 pg/ml). For the same patients, the mean baseline E1 levels of 33.8 +/- 2.4 pg/ml and 28.5 +/- 4.7 pg/ml were also not significantly different. The mean body weight of the tumor patients (141.1 +/- 7.3 lbs.) was similar to the mean weight of the non-tumor subjects (137.5 +/- 6.3 lbs.). This was of importance since both E2 and E1 levels correlated significantly with body weight and excess fat in these postmenopausal women. The circulating estrogen levels did not correlate significantly with the patients' height, age, or years of menopause. In the patients with endometrial cancer the mean E2 (14.1 +/- 1.7 pg/ml) and E1 (39.5 +/- 7.3 pg/ml) levels after ovariectomy were not significantly different from the preoperative concentrations. These data are consistent with the concept that in postmenopausal women most, if not all, circulating estrogen is produced by peripheral conversion of androgens and that this conversion is influenced by obesity. Circulating estrogen levels are not significantly different in postmenopausal patients with endometrial cancer compared with women of a similar age and weight who do not have the tumor.

Circannual cycle in plasma testosterone levels in man.

Abstract: In a group of 15 healthy male subjects a statistically significant circannual cycle in plasma testosterone levels was assessed by sampling blood at 3-monthly intervals. Peak levels were found in summer and early autumn and a nadir in the winter and early spring.

Aromatization of androstenedione by cultured human fibroblasts

Abstract: The conversion of [l,2,6,7-3H]androstenedione to [3H]estrone was measured in fibroblast monolayers grown from biopsies of genital and nongenital skins obtained from 15 control subjects, 9 males with developmental defects of the urogenital tract, and8 patientswith hereditary male pseudohermaphroditism. Under the standardized conditions utilized in this study, the rate of estrone formation in the fibroblasts from normal controls varied from < 0.2 to5.5 pmol/100 mg protein/h, and these rates were enhanced by incubation of intact monolayers with choleragen, theophylline, or dexamethasone. Rates of estrone formation were higher insome foreskin strains grown from subjects with developmental defects of the urogenital tract andinstrains from scrotum and foreskin of patients with familial incomplete male pseudohermaphroditism, types 1 and 2 than in normal strains or strains from patients with testicular feminization. Themeaning of these apparent high rates of estrone formation is unclear.

Intestinal metabolism of estrogens.

Abstract: Estrogen metabolism in the human intestine was studied in two ways. Firstly, by measuring the excretion of 12 estrogens in pooled human late pregnancy feces before and during the administration of ampicillin (2 g/day). Secondly, by administering 5.4 and 20 mg of 16α-hydroxyestrone orally to two postmenopausal women and analyzing the estrogens in simultaneously drawn portal and peripheral venous blood samples at time intervals from 0 to 150 min after steroid administration. The majority of the estrogens in normal pregnancy feces were unconjugated. The amounts of estradiol, estrone and 16-epiestriol excreted, relative to the principal estrogen estriol, were greater than in pregnancy bile or urine and 16α-hydroxyestrone, an important biliary estrogen, was only present in trace amounts. Considerable quantities of 15α-hydroxyestradiol-17β were also found. Ampicillin administration, which decreases intestinal bacterial steroid metabolism, caused a huge increase in the fecal excretion of conjugated estr...