Search

The effects of garlic supplementation on protein metabolism were investigated by measuring testis testosterone and plasma corticosterone in rats fed diets with different protein levels. In Experiment 1, rats were fed experimental diets with different protein levels (40, 25 or 10 g/100 g casein) with or without 0.8 g/100 g garlic powder. After 28 d of feeding, testosterone contents in the testis were significantly higher and plasma corticosterone concentrations were significantly lower in rats fed 40 and 25% casein diets with garlic powder than in those fed the same diets without garlic powder. Urinary excretion of 17-ketosteroid (an index of testosterone), nitrogen balance and hepatic arginase activity were significantly higher in rats fed the 40% casein diet with garlic powder than in the 40% casein controls. In Experiment 2, the effect of diallyldisulfide (a major volatile sulfur-containing compound in garlic) on the secretion of luteinizing hormone (LH) from the pituitary gland, which regulates testosterone production in the testis, was investigated in anesthetized rats. Plasma LH concentration increased dose dependently after administration of diallyldisulfide (P < 0.01, r = 0.558). These results suggest that dietary supplementation with 0.8 g/100 g garlic alters hormones associated with protein anabolism by increasing testicular testosterone and decreasing plasma corticosterone in rats fed a high protein diet.

A 28-year old female patient with virilization due to left adrenocortical adenoma was studied. The patient had clinical features of hyperandrogenism such as hirsutism and a low pitched voice, but not of hypercorticoidism. Plasma testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were high. Although the basal plasma cortisol concentration and urinary excretion of 17-hydroxycorticosteroids (17-OHCS) were within the normal range, the absence of diurnal variation in plasma cortisol and loss of suppressibility by dexamethasone suggested constitutive secretion of cortisol by the tumor. Inappropriate cortisol secretion was also supported by blunted ACTH response to provocative stimuli. After successful removal of the left adrenal tumor, such endocrinological abnormalities were all normalized. Immunohistochemical analysis revealed that tumor cells were positively stained for C21 hydroxylase cytochrome P-450 (P-450C21) and P-450(11) beta which convert 17-hydroxy (OH) progesterone to cortisol as well as P-450SCC, 3 beta-hydroxysteroid dehydrogenase and P-450(17) alpha which are involved in testosterone biosynthesis. These findings suggest that adrenocortical adenoma secretes predominantly testosterone and constitutively cortisol in a young woman patient with virilization.

We report the hormonal and radiological evaluation of two cases of adrenal cortical adenomas that secreted testosterone exclusively. We discuss some of the pitfalls in the diagnosis of this lesion, and summarize the current knowledge of the characteristic hormonal features in the two cases and the 12 cases previously reported.

Using a newly devised radioligand method for the simultaneous determination of urinary testosterone (T) and androstanediol (Adiol) nine girls with precocious adrenarche were evaluated. In the base-line state average urinary T excretion (1.29 mug/24 hr) and Adiol excretion (1.33 mug/24 hr) were significantly elevated when compared with 15 age-matched controls (0.3 and 0.33 mug/ 24 hr, respectively, P less than 0.001 for both). Adrenocorticotropic hormone (ACTH) infusion performed in five patients with precocious adrenarche produced at least a 50 greater than increase in urinary T excretion in all and a similar increase in Adiol excretion in four of five patients. Dexamethasone administration in the same five patients produced a 25 greater than fall in urinary T excretion in all and a comparable fall in Adiol in four.

A 27-yr female patient was admitted to the hospital because of secondary amenorrhea and a severe and complex virilization syndrome. The urinary 17-Ks, 17 OHCS and testosterone glucuronide values were greatly increased. The plasma testosterone through very high, was within the normal limits in males (3.52 ng/ml). Urography, echography and CT scan revealed a large right adrenal tumor. Removal of the tumor brought about a considerable clinical improvement: reoccurrence of the menstrual cycle, a progressive decrease in the virilization syndrome and normalization of the urinary 17-Ks, 17-OHCS and of the plasma testosterone.

We have previously reported increased testosterone and androstenedione concentrations and decreased sex hormone binding globulin (SHBG) concentrations in the plasma of massively obese women. We now report that these plasma hormone concentrations return to normal in twelve of the same women after substantial weight reduction and these changes are associated with more normal menstrual cycles. We conclude that body weight and fat are important determinants of sex steroid secretion and binding and thus influence menstrual function.

Both pregnenolone and 17-OH-pregnenolone were found to be higher in the plasma of patients with poorly controlled congential adrenal hyperplasia than in normal subjects. The plasma levels of these precursor steroids were significantly correlated with urinary 17-ketosteroid and pregnanetriol excretion and with plasma testosterone. The mechanism where by plasma pregnenolone and 17-OH-pregnenolone levels are elevated in patients with 21-hydroxylase deficiency is unknown, but the phenomenon of product inhibition is suggested as a possible explanation. As 17-OH-pregnenolone in plasma is almost entirely of adrenal origin, its measurement promises to be useful in the management of patients with congenital adrenal hyperplasia. Acute stimulation with ACTH caused negligible changes in the plasma levels of pregnenolone and 17-OH-pregnenolone and failed to distinguish between overly, appropriately, and under-treated patients. However, following repeated stimulation with repository ACTH, the steroid levels rose. These findings indicate limited adrenal responsiveness to ACTH following chronic glucocorticoid treatment of congenital adrenal hyperplasia, even in under-treated patients, and suggest that normal precursor steroid levels in plasma and normal 17-ketosteroid and pregnanetriol excretion can only be achieved by the suppression of total steroidogenesis to less than that occurring in normal subjects.

A double blind, controlled study was carried out in order to investigate the effects of administering spironolactone, 200 mg daily, to five healthy male volunteers. The patterns of change in plasma testosterone (T) and luteinizing hormone (LH) after spironolactone were significantly different from placebo and there were significant increases in the urinary excretion of androsterone (A), aetiocholanolone (EC) and total oestrogen. Urinary dehydroepiandrosterone (DHA) excretion, after an initial rise, declined progressively during the treatment period relative to controls. The results are discussed in the light of previous observations. It is concluded that treatment with spironolactone for 2--4 days will lead to a transient rise in plasma T and urinary DHA. Continued treatment (4--10 days) is thought to cause increased LH secretion, with normalization of plasma T and DHA excretion. These changes are accompanied by increased androgen catabolism and a slightly increased conversion of androgens to oestrogens. Healthy men may therefore show alterations in sex steroid metabolism if treated for several days with high doses of spironolactone.

Hirsute women pose a diagnostic dilemma when urinary 17-ketosteroid and serum testosterone levels are normal. To locate the site of androgen excess in 19 hirsute women, blood samples were collested from the left ovarian and adrenal veins via a catheter insertedinto the right femoral vein. Laparoscopy and bilateral ovarian biopsies were also preformed in 18 of the 19 patients studied. Nine women had elevated 17ketosteroid (fivepatients) and/or antecubital serum testosterone (five patients) levels. Fourteen womanhad elevated testosterone concentrations distributed as follows: ovarian vein (six), adrenal vein (one), adrenal and ovarian veins (seven). Androstenedione was elevated in theovarian vein (seven) and both adrenal and ovarian veins (11) in 18 patients. Laparoscopic examinations revealed that less than 50 per cent of the enlarged ovaries could be detected by pelvic examination. Histologic studies suggested that these patients comprised two groups: a group (six patients) who appeared to ovulate and a group (12 patients) who lacked evidence of ovulation.

To evaluate the usefulness of blood testosterone (T) in monitoring the effects of therapy in congenital virilizing adrenal hyperplasia due to 21- or 11- hydroxylation defect (CVAH), T levels were measured on 45 occasions in 13 patients with CVAH; 32 urinary 17-ketosteroid levels and 31 preganetriol values were available for comparison. Bone age levels, growth data, and medication are listed to help assess the clinical state of the patient at the time of each T determination. Blood T values were above normal for age and sex in untreated patients with CVAH and declined with glucocorticoid suppression. A blood T value of 20 ng/100 ml appeared to distinguish between well-controlled cases and those with inadequate steroid suppression. Serial measurement of blood T in girls and in prepubertal boys with CVAH provides assistance in evaluating chemical control of the disease, particularly when accurate 24-h urine collections cannot be obtained for 17-ketosteroid and pregnanetriol assessments.

To determine whether a single morning plasma level of 17-hydroxyprogesterone (17OH-P), androstenedione, testosterone and progesterone reflected the degree of control of 21-hydroxylase congenital virilizing adrenal hyperplasia (CVAH) as indicated by 24-hour urinary 17-ketosteroid and pregnanetriol excretion, 142 simultaneous 24-hour urine and morning blood collections were made from 65 patients with CVAH. Patients were grouped into five categories on the basis of age, skeletal age, and sex. Paired blood and urinary data were analyzed. The results suggest that androstenedione is the most reliable indicator for all patient categories. Testosterone is an excellent indicator for children of both sexes and for adolescent and adult females. Levels of 17OH-P are difficult to interpret, as they can be several fold higher than the normal values when adrenal suppression appears adequate on the basis of urinary data. In general, progesterone is a poor indicator.

Urinary TG and fractionated 17-ketosteroid (Drosdowsky) determinations were performed before and after the intramuscular administration of 15,000 IU of human chorionic gonadotropin (hCG) in 10 sexually immature healthy boys and in 12 bilaterally cryptorchid boys. The same basal determinations were made in 11 gonadless girls. Basal serum FSH and LH were determined (by radioimmunoassay) in controls and also in cryptorchid boys. If 15mug/24 h (three SD's of basal excretion in controls) is considered the smallest adequate response, the TG but not the fractionated 17-KS determination assessed fairly well either the presence or the functional capacity of the Leydig cell-containing tissue. Agonadic girls had significantly higher basal excretion of steroids and this is presumably due to their greater absolute body size and to their more advanced bone age.

The research here reported concerns 9 hirsute women, four of them with PCO and five with idiopathic hirsutism, who underwent treatment with spironolactone. 4 non hirsute hypertensive cases served as control. For one year hair growth, testosterone, 17 Ks, estradiol and gonadotropins behaviours were studied in all of the patients. Results clearly show that the peripherical response (the hair) to the therapy is only just sufficient, and corresponds to a good reduction of the androgenic hormones in blood. However, there is also an LH gonadotropin secretion reduction which is statistically scarcely significant. If the therapeutic response of hair were good, fetal risk could be prevented with safe and contemporaneous contraception. However, since the response is scarcely sufficient, we do not think this therapy is more advisable than other ones.

Concentrations of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in serum and 17-ketosteroids (17-KS) in urine of 10 paraplegic and 10 quadriplegic subjects were measured from onset of injury and followed once a week for 4 months. Compared with age-matched normal controls, paraplegic subjects showed significantly lower serum levels of LH and FSH for 2 weeks and of testosterone for 6 weeks after spinal cord trauma, following which periods of time these hormones attained normal levels. By contrast, in quadriplegic subjects, serum testosterone concentrations remained significantly lower than those of the controls during the entire 4-month testing period. Furthermore, in another group of 10 chronic (1 to 6 years after onset of injury) paraplegic and 10 chronic quadriplegic subjects, serum testosterone and FSH concentrations were comparable to those of the normal controls. Serum LH concentrations were at control levels in chronic paraplegic but significantly depressed in chronic quadriplegic subjects. The concentrations of urinary 17-KS exhibited sharp fluctuations over the 4-month period and were below control levels in paraplegic but within control limits in quadriplegic subjects. The results indicate that the function of the hypothalamic-pituitary-gonadal axis is disturbed for at least 4 months in quadriplegic subjects.

Plasma testosterone levels were suppressed in 6 of 8 mature male patients with Cushing's disease, all of whom complained of loss of libido and decreased sexual potency. Gonadotrophin levels, both under basal conditions and in response to LH-RH, were generally normal. The testicular response to stimulation with hCG was brisk in the 2 patients examined. Oestradiol levels were slightly elevated in 2 patients and prolactin levels were normal in all patients. Thus, male patients with Cushing's disease demonstrated normal gonadotrophin levels in the presence of suppressed testosterone, or, viewed from a slightly different prospect, low testosterone levels despite normal gonadotrophins. Neither oestradiol nor prolactin excess appeared to account for the observations. Possible explanations for these findings include (a) a combination of impaired hypothalamic and testicular function, and (b) a resetting downwards of the level of testosterone that is seen as appropriate by the disordered bypothalamic-pituitary unit. Following correction of cortisol excess in Cushing's disease, testosterone levels rose into the normal range.

In 11 children aged between 2 and 17 years with (nonsalt-losing) congenital adrenal hyperplasia (21-hydroxylase deficiency) blood was drawn at 90-minute intervals during a 24-hour period and levels of 17-hydroxyprogesterone, testosterone, and cortisol were measured. Levels of 17-ketosteroids and pregnanetriol were measured too in 24-hour urine samples. These measurements were taken under different regimens of treatment and after interruption of treatment. Cortisol level rose and fell rapidly after administered corticosteroid, and reached unphysiologically high levels. Testosterone levels showed pronounced variations but stayed in the normal range for most of the time even in untreated patients; thus testosterone provides a poor control parameter. Levels of 17-hydroxyprogesterone showed extreme fluctuations and very high peak levels in untreated patients; standard treatment with two or three daily doses of corticosteroids did not prevent a pronounced rise in its level after midnight. After the first morning dose of hydrocortisone a very steep fall was observed. The 24-hour pregnanetriol excretion correlated well with the corresponding total integrated 17-hydroxyprogesterone area. It is concluded that single 17-hydroxyprogesterone values are unlikely to give adequate information about the quality of treatment.

To determine the most significant secretory source of their androgens, 13 hirsute nonvirilized women underwent selective bilateral adrenal and ovarian venous catheterization to obtain effluent blood for the assay of testosterone and delta4-androstenedione. In three patients the testosterone and delta4-androstenedione gradients were significantly greater in the adrenal venous effluents. Testosterone and delta4-androstenedione gradients were significantly greater in the ovarian venous effluents in four patients. In six patients there were no significant differences in the testosterone gradients between the adrenal and ovarian venous effluents. The delta4-androstenedione gradients were greater in the adrenal venous effluents in three of these patients, greater in the ovarian venous effluents in one, and not significantly different in two of these patients. The fact that the measurement of urinary 17-ketosteroid excretion, the suppressibility of peripheral plasma androgens with dexamethasone, and the stimulation of peripheral plasma androgens with human chorionic gonadotropin correlated poorly with the selective catheterization data suggests that the former modalities are imprecise in the diagnostic evaluation of hirsutism in women.

The effects of burn trauma in men on the production of adrenal and testicular steroids was investigated. Whereas there were significant increases in serum cortisol levels and urinary 17-hydroxycorticosteroid excretion soon after thermal injury, there were significant decreases in serum dehydroepiandrosterone sulfate, dehydroepiandrosterone, androstenedione, and testosterone concentrations during the first 4 weeks following burn trauma. Serum androstenediol and androstenediol sulfate levels also were reduced, though insignificantly, 10-23 days postburn. Serum LH levels were unchanged during the postburn interval. Since urinary 17-ketosteroid excretion was normal or below normal rather than increased, the decline in serum C19-steroid levels probably resulted from decreased glandular secretion rather than increased rates of metabolism and excretion. Low dehydroepiandrosterone sulfate and/or testosterone levels were found in some men several months after recovery from their burns. These data suggest that thermal injury leads to acute inhibition of adrenal and testicular C19-steroid secretion, but stimulation of adrenal glucocorticosteroid production, and that endocrine function in many instances is not normalized after complete healing of the burned surfaces. The mechanisms and physiological consequences of such changes in the steroid milieu of men after burn trauma are unknown.

Considering the larynx as a hormone dependent secondary sex characteristic has previously led to successful antiandrogentherapy of pachydermia of the vocal cords, which may constitute a precancerous state. As a first step to further evaluate the endocrine state of patients with precancerous lesions or cancer of the larynx, the urinary excretion of 17-hydroxysteroids, 17-ketosteroids, testosterone and estrogens has been determined in male patients with pachydermia laryngis (n = 15) or cancer of the larynx (n = 20) as compared to controls with different other otorhino-laryngological affections (n = 20). No difference between groups was found in 17-hydroxysteroids and no significant difference in 17-ketosteroid excretion. The pachydermia group as a whole showed significantly increased levels of testosterone (p = 0.01) and estrogen (p = 0.04) of 64.6 +/- 39.9 microgram/24 hr testosterone versus 34.7 +/- 19.3 microgram/24 hr in controls and 31.7 +/- 16 microgram/24 hr in laryngeal cancer and 277 +/- 14.8 microgram/24 hr total estrogens versus 19.1 +/- 12 microgram/24 hr and 17.8 +/- 8.1 microgram/24 hr respectively. These data further support the idea of hormonal factors playing an important role in the pathogenesis of pachydermia and thus possibly cancer of the larynx. So far, however, they do not permit definite conclusions on the pathogenetic mechanisms involved.

Significantly decreased levels of serum testosterone from the pre-anaesthesia level were found during and up to 7 days following major surgery under general anaesthesia (nitrous oxide, oxygen and halothane following induction with thiopental and succinylcholine chloride) in 18 male patients. On the other hand in the same patients, the serum lutenizing hormone (LH) increased significantly from the pre-anaesthesia level 30 min and 1 h after the beginning of anaesthesia. A slight increase in LH level was also noted on the 7th post-operative day. The determinations of serum testosterone and LH in fiberoptic bronchoscopy under the same general anaesthesia as that used in surgery or local anaesthesia in 26 male patients, revealed that the change in the serum LH during and following surgery seemed to be mainly induced by the general anaesthesia and that the rate of decrease in the serum testosterone may be related to the severity of surgical stress including the anaesthesia. The rate of increase in serum testosterone following the injection of gonadotrophin in 20 males on the 6th post-operative day was similar to that in 10 pre-operative males. The effects of pulmonary lobectomy on serum testosterone and urinary steroids were also studied in 6 males under adrenal suppression with dexamethasone. On the 6th post-operative day, the urinary aetiocholanolone plus androsterone and serum testosterone were found to be half the level of those on the pre-operative day, while the urinary 5beta-pregnane-3alpha, 17alpha, 20alpha-triol remained unchanged. These observations in human are not inconsistent with the report of Tcholakian and Eik-Nes (1971) in dogs namely that a shift in androgen biosynthetic pathway is present in the testis under surgical stress.

Two brothers with Reifenstein syndrome underwent LH-RH and HCG tests at various ages ranging from 13 to 17 years. We found that at age 13 the plasma LH and FSH response to one LH-RH injection was normal. After the age of 14, the basal plasma concentration of LH and FSH and their response to LH-RH became elevated. Concomitantly the plasma testosterone levels rose to abnormal levels. These findings are compatible with progressive development of primary gonadal dysfunction and with peripheral insensitivity to testosterone.

The study presents the data gathered along the years on the antisteroid action of the pineal gland. Thus, it was demonstrated that administration of pineal polypeptides to the rabbit lowers the urinary 17-KS both of testicular and adrenal origin. Conversely, pinealectomy caused an increase in the level of these steroid hormones. The same pineal material induced a marked decrease both in the serum and testicular testosterone and in the plasma and adrenal corticosterone in the rat. At the same time administration of pineal polypeptides lowered the cholesterol in the serum, bile, liver, testis and adrenal. Melatonin had no effect on these biochemical indices, which demonstrates that the effects obtained with pineal polypeptides are not mediated by melatonin.

Three children with Fanconi's anemia belonging to a family where 6 children had the disease were investigated. One child had growth hormone deficiency, a second child showed subnormal response of testosterone to gonadotropin stimulation and the third child had a missing insulin release following arginine. This report shows that growth hormone deficiency is not necessarily liniked with Fanconi's anemia when it occurs in a family. Multiple endocrine insufficiencies do no appear to be part of the disease.

Plasma follicle stimulating hormone, luteinizing hormone, testosterone, urinary 5-hydroxyindole acetic acid and 17-ketosteroids were measured in patients seen at an infertility clinic. Plasma follicle 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. 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.

The authors present four cases of operatively confirmed anorchism. The plasma levels of testosterone and 11-deoxy-17-ketosteroids and dehydroisoandrosterone in urine were low in all cases. After stimulation with HCG, plasma testosterone levels increased in two cases and did not change in another two. The levels of 11-deoxy-17-ketosteroids and dehydroisoandrosterone in urine did not increase.

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.

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.

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.

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.

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.