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The administration of human chorionic gonadotrophin (HCG) to dexamethasone-suppressed men caused parallel changes in the concentration of plasma testosterone and in the urinary output of androsterone+aetiocholanolone, total 17-oxosteroids and oestrogens. Discrepant results occurred in only four of the thirty-seven men tested. With these exceptions, the response to HCG could by followed as well by measuring androsterone+aetiocholanolone, 17-oxosteroid or oestrogen excretion rates as by following plasma testosterone levels. The most sensitive index of response was the rate of appearance of oestrogens in urine, and the next that of androsterone+aetiocholanolone.

The aim of the study was clinical evaluation of a new marker of pituitary tumours--the alpha subunit of glycoprotein hormones. The studies were performed in 152 patients with manifestations of intersellar tumours; an elevated serum alpha subunit concentration was found in 49 of these cases. The determinations of alpha subunit were performed by double antibody radioimmunoassay. Iodination of alpha subunit was made by chloramine T technique with subsequent purification of Ultrogel AcA54 column. The remaining pituitary hormones were also determined by radioimmunoassay. The incidence of pituitary tumours of alphoma type was 30 percent. Tumours occurred frequently in association with an increased serum growth hormone and manifestations of acromegaly, less frequently with hyperprolactinemia and signs of prolactinoma. Following neurosurgery of 60Co pituitary irradiation hypopituitarism was of high occurrence.

We present an unusual patient with a Leydig cell tumor to show that greatly elevated serum concentrations of 17-hydroxyprogesterone (17OHP) may not be diagnostic of congenital adrenal hyperplasia (CAH). A 3.5-yr-old boy had a small testicular mass and plasma 17OHP concentrations of 147-333 nmol/L (4,850-11,000 ng/dL), suggesting CAH with adrenal rests. However, normal plasma cortisol values and the unresponsiveness of the 17OHP concentration to dexamethasone suppression or ACTH stimulation suggested a diagnosis of Leydig cell tumor. A 4-fold elevation in plasma 21-deoxycortisol compared with a 200-fold elevation in 17OHP suggested that the elevated 17OHP derived from the normal pathway of testosterone synthesis in the testis. This was proven by normalization of all hormonal values after tumor resection. Compared to the abundance of mRNA for P450c17, the tumor contained unusually large amounts of mRNA for P450scc, the cholesterol side-chain cleavage enzyme, which is the rate-limiting step in steroid hormone synthesis. Increased P450scc activity, which increased the conversion of cholesterol to pregnenolone, apparently permitted the 17,20-lyase activity of P450c17 to become rate limiting, thus accounting for the increased secretion of 17OHP. Thus, Leydig cell tumors can produce quantities of 17OHP previously reported only in CAH due to 21-hydroxylase deficiency. The molecular characterization of steroidogenic mRNAs in this tumor indicates an unusual ratio in the expression of the genes for the steroidogenic enzymes, probably accounting for the unusual pattern of serum steroids.

Fifty-two children, age 5-10, from acne-prone families, were studied for a period of 1 year to examine the interrelationship between sebum, acne, pubertal development, and urinary steroid excretion. In each of the subjects, 30 boys and 22 girls, the composition of forehead skin lipid was determined 4 times yearly by thin-layer chromatography, with measurement of triglycerides, diglycerides, free fatty acids, wax esters, squalene, cholesterol, and cholesterol esters. Twice yearly, examination was made of the presence or absence of acne, pubertal maturation and the 24-hour urinary excretion of testosterone as determined by radioimmunnoassay, and of total 17-ketosteroids, dehydroepiandrosterone, androsterone, and etiocholanolone, as determined by paper chromatography. The relative amount of sebaceous lipids was positively correlated with age of the subjects (wax esters p less than .001, squalene p less than .05), as was the triglyceride-diglyceride component (p less than .05). No significant correlation was seen with the fatty acids. Acne, primarily comedonal, occurred in 27/52 subjects (15 girls, 12 boys) and was associated with higher sebum values. One-half of the children with acne had no signs of pubertal development. A significantly positive correlation was observed between the relative amount of sebaceous lipid and the urinary excretion of 17-ketosteroids, androsterone, and etiocholanolone in both sexes, and of testosterone and dehydroepiandrosterone in boys. The development of acne in children is an early pubertal event, often evident before other signs of pubertal maturation, and it is associated with an increase in sebum and in the urinary excretion of androgenic steroids.

Oral testosterone undecanoate (TU) in arachis oil has been evaluated with a view to its possible use as a means of androgen replacement therapy. A single 100 mg dose was found to elevate plasma androgen levels and urinary 17-ketosteroid excretion in 6 normal men. Ninety mg/day and 60 mg/day doses taken by a hypogonadal man resulted in sustained levels of androgen which appeared physiological when measured by radioimmunoassay without chromatography. However, upon separation of the steroids by chromatography it was found that much of the androgen present was in fact dihydrotestosterone not testosterone. Both TU and dihydrotestosterone undecanoate were detected in plasma by gas chromatography and it is suggested that the ester is absorbed as such from the intestine and the unesterified steroid subsequently released by hydrolysis. The convenience of oral administration, the resulting prolonged elevated plasma androgen levels and the probable lack of deleterious effects on the liver may render oral TU of value where androgen replacement therapy is indicated.

The mean basal plasma testosterone level in 28 patients with chromatin positive Klinefelter's syndrome was significantly lower than in 58 healthy male controls. In 12 of the patients the hormone levels were in the normal range. In both the eugonadal males and the Klinefelter patients the plasma testosterone levels spontaneously decreased throughout the day, the relative decrease in both groups being of the same order of magnitude. Short term ACTH infusion and the administration of dexamethasone did not significantly influence the plasma testosterone concentration in the Klinefelter patients. These findings do not support the view that the adrenal cortex plays a major role in contributing to the circulating plasma testosterone levels in this syndrome.

Twentyfour hour-urinary 17-oxo-steroids (17 KS), epitestosterone (ET) and testosterone (T) were measured before and after a 5-day-HCG-stimulation test performed in 65 healthy male volunteers aged 30 to 76 years. Subjects whose basal urinary T was higher than average physiological values showed a lower increase (p less than 0,001) in ET excretion rate after HCG stimulation than the rest of the casuistry. Neither T nor 17 KS increase after HCG stimulation showed any significant differences in the two subgroups. As ET behaves differently as compared both to the typical testicular androgen, and to the testicular-adrenal metabolites, the adrenal glands may not be the only nor even the main source of ET in the urine of healthy men.

Plasma follicle stimulating hormone, luteininzing hormone, testosterone, urinary 5-hydroxyindole acetic acid and 17-ketosteroids were measured in patients seen at an infertility clinic. Plasma folicle stimulating hormone and luteinizing hormone levels, and urinary 5-hydroxyindole acetic acid levels were increased in patients with sperm concentrations less than 10 times 10(6) per ml. Plasma testosterone levels were lower in patients with sperm concentrations less than 10 times 10(6) per ml. The results suggest that in patients with sperm counts less than 10 times 10(6) per ml. there is not only impaired spermatogenesis but also decreased Leydig cell function. Urinary 17-ketosteroid levels were not related to sperm cell concentration.

Seven oophorectomized patients were administered a total of 60,000 units of human chorionic gonadotropin over a 3-day period, and plasma testosterone levels were obtained. One of the 7 patients demonstrated a definitive response to the hormone but repeat testing proved to be negative. The potential role of luteinizing hormone in the pathogenesis of polycystic ovarian syndrome is discussed and current evidence linking LH to adrenal androgenesis is reviewed. Modifications that may be employed for future study are suggested.

Alterations of sexual hormones in plasma of ageing males occur between the 50th and 60th year of life with individual variations: 1. Decreased values of testosterone in plasma and a poor response to gonadotrophins demonstrate a diminished synthesizing capacity of the testes in old men. 2. The decreased testosterone plasma values are followed by an increase in LH. The response of the anterior pituitary gland to LH-RH stimulation in old men is normal. 3. Under basal conditions estrone as well as estradiol plasma concentrations increase significantly with age because of increased conversion from androgens. 4. Parallel to estrogen plasma values an increased concentration of the sexual hormone binding globulin (SHBG) is found, resulting in a steep decrease of the free (= active) testosterone fraction. 5. Decreased testosterone, which is more strongly bound to SHBG and increased estrone and estradiol plasma values result in an androgen/estrogen imbalance in old men.

A patient with virilization was studied. The basal urinary excretion of 17-ketosteroids was at the upper limit of normal, but the plasma testosterone concentration was greatly elevated. Testosterone secretion could be stimulated by hCG, suppressed by dexamethasone, and was not affected by ACTH. At operation, an arrhenoblastoma of the left ovary was found. Isolated tumor cells in culture secreted testosterone. The addition of a LRH agonist (10 ng/ml) suppressed the secretion of testosterone by 50% (P less than 0.01). The inhibiting effect of a LRH agonist on steroidogenesis suggests that LRH receptors were present on this tumor and that treatment with LRH agonists might be beneficial in patients with metastatic steroid hormone-secreting ovarian and testicular tumors.

Interactions between gonadal hormones and adrenocortical function have been studied in the male rat. After injection (im) of testosterone, the accessory reproductive organs are more stimulated in the castrated rats than in the castrated adrenalectomized rats. Gonadectomy increases lipids, cholesterol and corticosterone in adrenal glands and plasma corticosterone levels. Testosterone reverses these effects.

The steroid response of testes to exogenous gonadotropin administration was studied before castration in a patient with the complete form of the testicular feminization syndrome. Urinary steroid determination were made along with measurements of plasma testosterone during adrenal suppression with dexamethasone and after stimulation with human menopausal gonadotropin (HMG) and HMG plus human chorionic gonadotropin (HCG). Our data provide evidence that the gonads in the testicular feminization syndrome synthesize steroids normally. Estrogens and testosterone are secreted by the testes, and the Leydig cells of the testes are capable of responding to exogenous HMG and HCG stimulation. These findins are consistent with the hypothesis that there is no abnormal testicular steroidogenesis in these genotypic males. Additional evidence is provided that these gonads secrete testosterone in amounts comparable to those of normally functioning testes. Failure of virilization in the presence of androgen secretion as indicated by previous authors is probably the result of a deficiency of androgenic action at the end organs. The presence of sparse pubic and axillary hair in the mother and the finding of the same type of karyotype (46,XY) in a sibling suggest that hereditary factors play a role in this disorder.