Leptin, insulin and TNF-alpha in weight loss.

Forty-eight morbidly obese patients were placed on a very low calorie (800 kcal) formula diet (OPTIFAST) for a 10-week period with the goal of achieving 10% weight loss within this time. Weekly serum leptin measurements were performed to determine whether changes in this adipose protein would serve as a useful marker of acute and chronic weight loss compliance. In the basal state, serum leptin averaged 56.

Short-term modulation of the androgen milieu alters pulsatile, but not exercise- or growth hormone (GH)-releasing hormone-stimulated GH secretion in healthy men: impact of gonadal steroid and GH secretory changes on metabolic outcomes.

Gonadal steroids are known to alter GH secretion as well as tissue metabolism. The present study was designed to examine the effects of short term (2- to 3-week) alterations in gonadal steroids on basal pulsatile (nonstimulated) and exercise- and GH-releasing hormone-stimulated GH secretion, urinary nitrogen excretion, and basal and exercise-stimulated oxygen consumption. Two protocols were conducted, which reflect a total of 18 separate studies.

Differential sex steroid negative feedback regulation of pulsatile follicle-stimulating hormone secretion in healthy older men: deconvolution analysis and steady-state sex-steroid hormone infusions in frequently sampled healthy older individuals.

The healthy aging male reproductive axis tends to exhibit a progressive decline in serum concentrations of biologically available testosterone with gradual concomitant reciprocal increases in both LH and FSH concentrations. However, relatively little is known about the sex steroid-mediated negative feedback regulation of physiologically pulsatile gonadotropin release in general, and episodic FSH release in particular, in older males. To examine the steroid hormone negative feedback control of pulsatile FSH secretion in healthy older men, we applied multiparameter deconvolution analysis to serum FSH (immunoradiometric assay) profiles obtained by sampling every 10 min over 24 h during steady state (4.

Alterations in pulsatile luteinizing hormone and follicle-stimulating hormone secretion in idiopathic oligoasthenospermic men: assessment by deconvolution analysis--a clinical research center study.

To investigate the nature of neuroendocrine disturbances of the hypothalamo-pituitary-gonadal axis in idiopathic male infertility, we studied 14 infertile men with oligoasthenozoospermia (OLIGO) and 15 age-, body mass index-, and community-matched euspermic controls by blood withdrawal at 10-min intervals for 12 h to encompass basal (8-h) and exogenous GnRH-stimulated (4-h) pulsatile release of LH and FSH (by immunoradiometric assay) as well as testosterone (by RIA). Deconvolution analysis was used to estimate endogenous LH and FSH half-lives, secretory burst frequency, amplitude, duration, and mass. OLIGO men exhibited normal serum concentrations of total, free, and percent dialyzable testosterone and estradiol, but distinct dynamic alterations within the LH and FSH axes; namely (P < 0.

Neuroendocrine alterations in the somatotropic and lactotropic axes in uremic men.

To investigate the pathophysiology of altered growth hormone (GH) and prolactin secretion in endstage renal disease, we sampled blood at 10-min intervals for 24 h and applied deconvolution analysis to calculate hormone half-lives and pulsatile secretion rates. Two-site immunoradiometric assays were employed to quantitate presumptively intact GH and prolactin in nine middle-aged men with chronic renal failure and 14 gender-, age-, body weight- and community-matched controls. We observed that the half-lives of endogenous GH and prolactin were prolonged significantly in uremia: for GH, control 17 +/- 1.

Changes in the hypothalamic-pituitary-gonadal axis in men after cadaver kidney transplantation and cyclosporine therapy.

A variety of plasma androgens, estradiol, follicle-stimulating hormone, luteinizing hormone, prolactin, cortisol, and thyroid parameters were examined in 10 men followed serially before and after cadaver kidney transplantation. Before transplantation, plasma testosterone levels were below normal in 8 of the 10 men. Free testosterone, follicle-stimulating hormone, and luteinizing hormone were at the lower range of normal values, yet plasma estradiol levels were elevated 3-fold, and prolactin levels were also high.

Augmented growth hormone (GH) secretory burst frequency and amplitude mediate enhanced GH secretion during a two-day fast in normal men.

Serum GH concentrations are increased in fasted or malnourished human subjects. We investigated the dynamic mechanisms underlying this phenomenon in nine normal men by analyzing serum GH concentrations measured in blood obtained at 5-min intervals over 24 h on a control (fed) day and on the second day of a fast with a multiple-parameter deconvolution method to simultaneously resolve endogenous GH secretory and clearance rates. Two days of fasting induced a 5-fold increase in the 24-h endogenous GH production rate [78 +/- 12 vs.

Treatment of hirsutism in women with flutamide.

Objective: To explore the clinical usefulness of the antiandrogen flutamide in the treatment modality for hirsutism in women.

Design: Nine women with hirsutism were assessed before and then monthly for 3 months on a regimen of flutamide 250 mg three times a day as the sole therapeutic agent. Blood samples were taken at each assessment time for a battery of androgenic parameters.

Sex hormone metabolism in upper and lower body obesity.

Morbid obesity has been previously shown to be associated with excessive production and metabolism of a variety of androgens and estrogens. Further, SHBG is lowered, resulting in high levels of 'free' testosterone. We have re-examined these parameters in morbidly obese women with upper vs lower body adipose distribution.

Androgen-estrogen metabolism in women with upper body versus lower body obesity.

Androgen and estrogen production rates were examined in 29 morbidly obese women with upper or lower body obesity. Although blood production rates of testosterone (T), dihydrotestosterone, and androstenedione (A4) were elevated in all of these women, those with upper body obesity (waist-height ratios, greater than 0.85) had higher T and production rates than women with lower body obesity (waist-height ratio less than 0.

Monthly cyproterone acetate in the treatment of hirsute women: clinical and laboratory effects.

Cyproterone acetate given as a single intramuscular dose of 300 mg monthly for 6 months resulted in significant reduction of hirsutism without appreciable side effects. This regimen resulted in decreased levels of luteinizing hormone (LH) and estradiol in the eight women studied. No significant changes were observed in total serum testosterone (T) levels, however, there was a reduction in sex hormone binding globulin (SHBG), resulting in lowered SHBG-bound T, and an increase in non-SHBG-T over this time.

Decreased 3 alpha-androstanediol glucuronide levels in plasma and random urines in male pseudohermaphroditism caused by 5 alpha-reductase deficiency.

Concentrations of 3 alpha-diol glucuronide (3 alpha-diol G) in plasma and/or random urine samples were determined in seven subjects with familial male pseudohermaphroditism (FMP) due to 5 alpha-reductase deficiency (5 alpha-RD). All subjects were natives of an isolated Turkish village with a high incidence of consanguineous marriage. A specific and sensitive antibody to 3 alpha-diol was used for radioimmunoassay of 3 alpha-diol G after hydrolysis and chromatographic purification.

Medical adrenalectomy for advanced prostatic cancer: clinical and hormonal effects.

We examined the effect of medical adrenalectomy on the clinical and hormonal responses in 50 men with disseminated prostatic carcinoma. Patients refractory to initial hormonal therapy were treated with aminoglutethimide and hydrocortisone (AG-HC) and evaluated by the criteria of the National Prostatic Cancer Project. Eight patients showed a partial response (PR), and 17 remained stable while receiving these medications.

Alterations in the pulsatile properties of gonadotropin secretion in alcoholic men.

The functional characteristics of the hypothalamic-pituitary-testicular axis were examined quantitatively in 10 chronic alcoholic men without hepatic dysfunction or clinical nutritional deficiencies. Spontaneous gonadotropin pulsatility was analyzed in blood sampled every 20 minutes over a 24-hour period 3 to 16 days after abstinence from alcohol and again 29 to 39 days later. The numbers of LH and FSH pulses per 24 hours were normal in these alcoholic men compared with controls.

Clinical usefulness of plasma androstanediol glucuronide measurements in women with idiopathic hirsutism.

Serum androstanediol glucuronide (3 alpha-diol G), a metabolite of the active androgens dihydrotestosterone and androstanediol, was elevated in 28 consecutive women with idiopathic hirsutism (IH). The mean 3 alpha-diol G level in the women with IH was 487 +/- 192 (+/- SD) ng/dL compared to 119 +/- 37 ng/dL in normal women (n = 50), and only 1 patient had a value overlapping with the normal range. Since 3 alpha-diol G appears to be formed entirely in target organs and has a long serum half-life, we studied its clinical usefulness by following women with IH during treatment.

Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations.

We undertook a study of the separate and combined effects of age and sex on the pulsatile pattern of GH secretion. The 24-h secretory profile of GH was generated by 20-min sampling in 10 young women (aged 18-33 yr), 10 young men (aged 18-33 yr), 8 postmenopausal women (aged greater than 55 yr), and 8 older men (aged greater than 55 yr). A computer-assisted pulse analysis program was used to assess both total GH secretion, as reflected in the 24-h integrated GH concentration (IGHC), and pulsatile secretion, as denoted by pulse frequency, duration, amplitude, and the fraction of GH secreted in pulses during the 24-h period (FGHP).

Endocrine impact of pure estradiol replacement in postmenopausal women: alterations in anterior pituitary hormone release and circulating sex steroid hormone concentrations.

Thirteen healthy postmenopausal volunteers were studied under basal conditions and at intervals (days 1, 5, 10, and 30) after intravaginal placement of a polysiloxane ring impregnated with 400 mg of estradiol. Mean serum estradiol concentrations rose 26-fold with a twofold increase in serum estrone concentrations. Serum delta 4-androstenedione, dehydroepiandrosterone sulfate, and total testosterone did not change, but absolute and percent free testosterone concentrations declined significantly by day 5.

Response of the prepubertal ovary to acute chorionic gonadotropin administration: absence of modulation by growth hormone.

Twenty-five short term hCG stimulation tests were performed in seven prepubertal girls, aged 3-11 yr, who were being evaluated for short stature. Provocative testing revealed GH deficiency in all patients, but reevaluation of one girl at a later date showed normal somatotropin levels. The study protocol lasted 18 months and included testing before, during, and after 1 yr of GH therapy.

Elevated production and metabolic clearance rates of androgens in morbidly obese women.

Blood production rates of testosterone, dihydrotestosterone (DHT), and 3 alpha-androstanediol (3 alpha-diol) were found to be approximately 2-fold elevated in morbidly obese, nonhirsute, normally menstruating women. Values were intermediate between those found in normal women and those in a group of nonobese normally menstruating women with idiopathic hirsutism. Elevated androgen production rates in obese women were associated with 2- to 3-fold increases in MCRs, presumably due to decreased levels of sex hormone-binding globulin.

Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

We have tested the participation of endogenous opiate pathways in the negative feedback actions of gonadal steroids on pulsatile properties of luteinizing (LH) hormone release in normal men. To this end, sex steroid hormones were infused intravenously at dosages that under steady state conditions selectively suppressed either the frequency or the amplitude of the pulsatile LH signal. The properties of pulsatile LH secretion were assessed quantitatively by computerized analysis of LH series derived from serial blood sampling over 12 h of observation.

Suppression of residual oestrogen production with aminoglutethimide in women following surgical hypophysectomy or adrenalectomy.

In postmenopausal women with breast carcinoma, plasma and urinary oestrogens remain detectable following surgical adrenalectomy or hypophysectomy. These residual oestrogens could result from absorption of exogenous steroids, from endogenous production, or from a combination of these two sources. To determine whether endogenous production contributes to this oestrogen pool, we administered a potent steroidogenesis inhibitor, aminoglutethimide (AG), to women with breast carcinoma following hypophysectomy or adrenalectomy.

A comparison of androgen production and clearance in hirsute and obese women.

Virilization in women is associated with increased production of testosterone as well as a variety of androgenic prehormones, including androstenedione, androstenediol, DHEA, DHEA-sulfate, dihydrotestosterone and androstanediol. Of these hormones, it is likely that testosterone is the androgen which initiates a series of androgen-receptor mediated events resulting in stimulation of 5 alpha reductase in the skin and hair follicles, producing dihydrotestosterone locally. The metabolism of testosterone to dihydrotestosterone within the hair follicle results in increased clearance of testosterone, however at the expense of hair follicle stimulation.

Clinical and biochemical effect of aminoglutethimide in the treatment of advanced prostatic carcinoma.

Treatment of male patients with advanced prostatic carcinoma and disease progression after initial endocrine therapy frequently is unsatisfactory. However, approximately 20 per cent of these patients respond to surgical adrenalectomy or hypophysectomy, indicating continued hormonal responsiveness. A total of 25 previously castrated men with stage D carcinoma received 1,000 mg.

Adequacy of estrogen suppression with aminoglutethimide and hydrocortisone as treatment of human breast cancer: correlation of hormonal data with clinical responses.

Human breast neoplasms can be divided into hormone-dependent and hormone-independent subtypes. Estrogen is the major hormonal stimulus for growth of the dependent tumors. Failure to respond to estrogen suppression therapy could reflect either an incomplete lowering of estrogens or the hormonal independence of the tumor.

In vivo and in vitro pharmacological studies of aminoglutethimide as an aromatase inhibitor.

Use of steroid biosynthesis inhibitors to suppress estrogen production is a logical strategy in the treatment of women with hormone-dependent breast cancer. The clinical availability of aminoglutethimide as an inhibitor of cytochrome P-450-mediated steroid hydroxylations prompted study of the precise pharmacological and biochemical effects of this drug. Pharmacokinetic studies revealed that aminoglutethimide alters its own metabolic clearance rate as well as that of dexamethasone, a synthetic glucocorticoid.