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Seven patients were studied with 24Na to determine the relative disappearance time of the isotope from the postmastectomy lymphedematous arm as compared to the normal side. The results tend to confirm previously held convictions that the edema is usually confined to the subcutaneous fat and skin. The disappearance time (T1/2) of the radioactive sodium from the muscle of the edematous side was usually comparable to that of the control side. The data also indicate that the impairment of fluid drainage from other areas, such as the lateral chest wall, that normally drain into the axilla, is impaired similarly to that of the subcutaneous fat of the arm. Operative procedures designed to relieve the edema of the arm by providing an alternate route of drainage should provide a conduit for the fluid to an area that does not normally drain to the axilla of the affected side.

Testosterone-1,2-3H was administered by vein to 7 subjects (3 with normal thyroid function, 2 with hyperthyroidism, and 2 hypothyroids) in order to measure the t ½ of testosterone in the circulation, to observe the distribution and disappearance of its principal radioactive conjugated 17-ketosteroid metabolites in the plasma, and to calculate the clearance rates of the individual conjugates. It was found that the t ½ of testosterone ranged from 60–80 min in the hyperthyroids as well as in an euthyroid subject. In all instances, the labeled glucosiduronates were removed from the plasma much more rapidly than were the radioactive sulfates, 65–90% of their maximum plasma radioactivity disappearing within 4 hr. In the sulfate fraction, androsterone sulfate persisted longer than etiocholanolone sulfate; only 13–22% of its maximum plasma radioactivity being removed at this time. These findings are consistent with the clearance rates (ml per min) of the individual conjugates: androsterone sulfate (0.5–4...

Plasma luteinizing hormone, follicle-stimulating hormone, and estradiol were measured at 20-minute intervals for 24-hours in seven pubertal premenarchal girls whose sleep was monitored polygraphically. A circadian variation in plasma estradiol was demonstrated with the highest values occurring during the day (1400-1600 hours) and lowest values during sleep, a time when gonadotropin secretion was augmented.

Plasma luteinizing hormone (LH) and testosterone (T) were measured by radioimmunoassay in nine pubertal boys and three sexually mature young men at 20-min intervals for 24 h. Plasma LH and T were also measured in one boy during a delayed sleep onset study. Polygraphic monitoring was carried out to identify precisely sleep onset. Wakefulness, and specific sleep stages. In all nine pubertal boys the plasma T concentration fluctuated and was significantly higher during normal nocturnal sleep as compared to daytime waking. This increased T secretion during sleep was temporally linked to the characteristic pubertal sleep augmentation of LH secretion. To define further the relationship of this increased T secretion to sleep, plasma LH and T were also measured in three of the pubertal boys after acute (1-day) reversal of the sleep-wake cycle. One of these boys was also studied after 3 days of sleep-wake cycle reversal. The results of these studies showed that plasma T was now augmented during the reversed daytime sleep period; the mean T concentrations during this period were significantly higher (P < 0.001) than during nocturnal waking in all four studies. Measurement of plasma LH and T in the three sexually mature young men showed episodic secretion of LH and T during both waking and sleep periods; there was no consistent significant augmentation of LH or T secretion during sleep. This study demonstrates that (a) in normal pubertal boys and sexually mature young men plasma T fluctuates episodically; (b) there is marked augmentation of T secretion during sleep in pubertal boys, which is dependent on increased LH secretion; (c) this pubertal LH-T secretory “program” is dependent on sleep, since it shifts with delayed sleep onset and reversal of the sleep-wake cycle; and (d) this demonstrable tropic effect of LH on T is evident only during puberty, since sexually mature young men fail to show any consistent relationship between LH and T secretion either awake or asleep.

Adrenocortical activity was studied in 19 emaciated women with anorexia nervosa. Relative to body size the patients' mean cortisol production rates of 0.591 mg/kg/day and 16.4 mg m2/day were significantly elevated compared to those of 0.322 mg/kg/day and 11.4 mg/m2/day for age and sex matched normal controls (p less than 0.001 and 0.02, respectively). The 24-hr mean plasma cortisol concentration in 18 patients was 10.6 microgram/dl and was significantly higher than that of the controls (6.8 microgram/dl, p less than 0.001). The average excretion of urinary free cortisol in nine patients was 205 microgram/day, significantly greater than that of 65 microgram/day in the controls (less than 0.01). Three patients underwent overnight suppression with 1 mg of dexamethasone and had inadequate responses. These data suggest that cortisol production is excessive in emaciated patients with anorexia nervosa due to a disturbance of the hypothalamic-pituitary mechanisms regulating adrenocortical function. The excessive adrenal activity may reflect certain psychobiological disturbances as well as the effects of malnutrition.

The present study describes the isolation from human urine and definitive chemical identification of 4 members of a new class of acidic metabolites of corticol, characterized by a 21-oic acid group: 3α, 17, 20α-trihydroxy-11-oxopregnan-21-oic acid; 3α,17,20β-trihydroxy-11-oxopregnan-21-oic acid; 3α,11β,17,20α-tetrahydroxypregnan-21-oic acid; 3α,11β,17,20β-tetrahydroxypregnan-21-oic acid; The trivial name “cortoic acids” is suggested for this group of metabolites; the individual compounds, named after the corresponding 21-hydroxy metabolites, would be: “cortolonic acid,” “β-cortolonic acid,” “cortolic acid” and “β-cortolic acid,” respectively. Together these metabolites constitute 5–25% (mean 12%) of the administered cortisol. The most abundant by far is “cortolonic acid” which is one of the 4 most abundant metabolites of cortisol. Transformation of cortisol to these metabolites involves an intramolecular shift of a hydrogen atom from C-21 to C-20 as well as oxidative removal of the other hydrogen...

To determine if the central nervous system "program" controlling PRL secretion is operative during pregnancy, three pregnant women (12th, 20th and 32nd week of gestation) had 24-hour, 20-minute interval plasma sampling and polygraphic monitoring of nocturnal sleep. All three subjects showed episodic PRL secretion during waking which became augmented during nocturnal sleep. Since the number of "major" PRL secretory episodes was similar to normals, the increased PRL levels were most probably achieved by increased secretion per secretory episode. These findings suggest that during pregnancy, the PRL sleep related secretory "program" is maintained in a qualitative manner, albeit at a higher set-point.

On 4 separate occasions 17–20 mg of cortisol was given intravenously for 4.5 to 6.5 hr at different times of the day to an adult male. Endogenous cortisol secretion was suppressed for 4.5–5.5 hr following cessation of the infusion, and was reinitiated after this period of suppression of secretory activity in a pattern similar to that observed during the same portions of the control days. The study supports the concept that the episodic 24-hr ACTH-cortisol secretory pattern is not directly determined by a sequence of high or low plasma cortisol concentrations, but rather regulated or “programmed” for recurrent shorter time periods linked to the 24-hr sleep-wake cycle.

The production rates of estradiol and cortisol in two male opiate addicts while on narcotic maintenance, were in the low normal or subnormal range. There was a sharp several-fold increase upon withdrawal with a subsequent fall to normal values after a period of abstinence. The changes in estradiol production rates were proportionally greater than those of cortisol and suggest that they were due to changes in testicular secretion of the precursor testosterone.

Twelve cancer patients and one patient with diabetes mellitus were treated with medroxyprogesterone acetate (MPA) by intramuscular injection in a total weekly dose of 400, 700, or 1200 mg. The treatment reduced the plasma cortisol concentration by 76% in the AM hours (21 leads to 5.0 mug/dl) and by 75% in the PM hours (12.8 leads to 3.2 mug/dl). Cortisol production rate decreased by 67% (19 leads to 6.2 mg/24 hrs). The 24 hour profile of plasma cortisol concentration measured in 3 patients showed zero secretion over this period. Low plasma ACTH values prevailed during treatment, and a blunted response to maximal ACTH stimulation was found. No evidence of adrenal insufficiency was observed in any patient, even though in some patients the plasma cortisol concentration remained at zero for many weeks. MPA has cortisol-like effects and the suppression of adrenal function is probably mediated by a negative feedback action on the hypothalamus or pituitary.The effects of medroxyprogesterone acetate (MPA), administered im in a total weekly dose of 400, 700, or 1200 mg, on the pituitary-adrenal axis were studied in 12 cancer patients and 1 patient with diabetes mellitus. MPA reduced mean A.M. plasma cortisol concentrations by 76% and mean P.M. cortisol concentrations by 75%. The 24-hour production rate of cortisol was reduced by 67%. 41% of the individual A.M. cortisol determinations and 61% of the individual P.M. determinations were not significantly (p greater than .001) different from 0. Plasma ACTH levels were low throughout treatment, and the response to maximal ACTH stimulation was not pronounced. Evidence of adrenal insufficiency was not observed in any of the patients. The results demonstrate the corticosteroid replacement properties of MPA, and it is suggested that the suppression of adrenal function is most likely mediated by a negative feedback action on the hypothalamus or pituitary.

Plasma LH, FSH and prolactin secretory patterns were derived from the measurement of 20-min interval plasma samples obtained during a complete 24-h period in a patient with persistent postpartum amenorrhe a and galactorrhea (Chiari-Frommel syndrome), before and after clomiphene citrate therapy. During nocturnal sleep, polygraphic monitoring was carried out to precisely identify sleep onset, specific sleep stages and waking periods. During the evening and nighttime hours, LH and FSH concentrations were markedly reduced, compared to the daytime patterns both before and after clomiphene therapy. A sleep-associated rise of prolactin concentration was present, similar to the pattern found in normal subjects but at higher concentrations. The reciprocal nature of the nocturnal secretory patterns for LH and FSH and prolactin in this patient suggests an alteration in hypothalamic dopaminergic mechanisms which are thought to control the secretion of these hormones.

The metabolism of 14C-testosterone was studied in 8 severely underweight young women with anorexia nervosa. The urinary androsterone/etiocholanolone (A/E) ratio was uniformly low, in a range characteristic of hypothyroidism; the patients also showed low plasma concentrations of triiodothyronine (T3). Clinical remission as manifested by weight gain was accompanied by concomitant increases of the A/E ratio and the plasma T, concentration to or toward normal. The administration of T3 also resulted in a shift of the A/E ratio toward normal. These data demonstrate that the low plasma T3 concentrations in patients with anorexia nervosa may be related to the development of one of the characteristic biochemical abnormalities found in clinical hypothyroidism, namely a decreased A/E ratio. These data suggest that the “low T3 syndrome” may be associated with biochemical hypothyroidism.

The 7-carboxymethoximino derivative of androsterone (1) has been prepared from dehydroisoandrosterone-17-ethyleneketal by a sequence involving inversion at C-3, introduction of a carbonyl at C-7, and reduction of the double bond at C-5. The substance was condensed with BSA by the carbodiimide procedure to afford a conjugate which produced anti-androsterone antiserum in innoculated rabbits. The antiserum is sufficiently active to be useful in radioimmunoassay procedures.

Prolactin secretion in normal adults is characterized by periods of episodic secretion which increase in magnitude during sleep. In this study, we report the 24-h mean prolactin concentrations, prolactin secretory patterns, and associated pituitary hormone function in nine patients (seven women and two men) with hyperprolactinemia of diverse etiologies. Four of the women and one of the men had clinically demonstrable pituitary tumors, one boy had a hypothalamic tumor, and the three other women had “functional” hyperprolactinemia. The 24-h mean prolactin concentrations derived from averaging the 20-min interval samples for 24 h ranged from 28.6 to 1,220 ng/ml. The plasma prolactin patterns in these patients showed persistence of episodic secretion in all and loss of the normal sleep-wake difference in plasma prolactin in seven of nine. Three of the patients with galactorrhea and comparable 24-h mean prolactin concentrations (58.3, 59.7, and 64.3 ng/ml) showed similar prolactin secretory patterns despite different etiologic mechanisms. Evaluation of the secretory patterns of luteinizing hormone (LH) in these patients showed loss of normal pulsatile LH release and a low 24-h mean LH concentration in the patient with the pituitary tumor, while the two patients without clinically demonstrable pituitary tumors (“post-pill” galactorrhea and “idiopathic” galactorrhea) showed normal LH secretory patterns and 24-h mean LH concentrations. The 24-h mean cortisol concentrations and secretory patterns were normal in five of the seven patients who had these parameters measured. The patient with the hypothalamic tumor had a low 24-h mean cortisol concentration and production rate and absent response to metyrapone. The patient with “idiopathic” galactorrhea had an elevated 24-h mean cortisol concentration but normal cortisol production rate and urinary 17-hydroxycorticoid excretion. Growth hormone secretion was abnormal in four of the patients (one with the hypothalamic tumor and three with pituitary tumors). Thyrotropin-releasing hormone (TRH) administration in four patients resulted in normal TSH release in two patients (one of whom developed galactorrhea after the test), an absent response in the patient with the hypothalamic tumor, and a blunted response in one of the women with a pituitary tumor. The two men had low 24-h mean plasma testosterone concentrations (69 and 30 ng/100 ml) and symptoms of impotence and loss of libido. Five of the women (four with pituitary tumors and one with Chiari-Frommel syndrome) had either low 24-h mean LH concentrations, abnormal LH secretory patterns, or both. These data indicate that patients with hyperprolactinemia encompassing a varied etiological range frequently show loss of the normal sleep-associated increase in prolactin secretion as well as abnormalities in the regulation of the other hypothalamic pituitary-regulated hormones. The finding that the abnormalities in LH, growth hormone, thyrotropin, and cortisol (adrenocorticotrophic) secretion were almost uniformly confined to the patients with the clinically demonstrable hypothalamic or pituitary tumors suggests that the size of the lesion is the critical factor.

The effect of flutamide on cortisol metabolism was studied in eight patients with prostate cancer. Flutamide markedly decreased the formation of 3 alpha, 17,21-trihydroxypregnane-11,20-dione (THF), and the 11-oxy-17-ketosteroid metabolites by 72%, 50%, and 46% respectively; however, 3 alpha, 11 beta, 17,21-tetrahydroxy-5 alpha- pregnan-20-one was increased by 46%. The 24-h mean plasma cortisol concentration was not altered. The cortisol production rate decreased by an average of 53% (from 32.7 to 15.5 mg/24 h). The effect of the drug on plasma cortisol kinetics was studied in three patients. This showed that flutamide increased the t1/2 (from 80 to 108 min) but decreased the distribution volume (from 17.8 to 13.8 liters) and the MCR (from 222 to 130 liters/24 h). The changes in THE and THF formation and in the t1/2 and MCR of [C]cortisol are similar to the effects observed in patients with intrahepatic cholestasis. It is suggested that in the case of flutamide these changes were also due to a cholestasis-producing effect of the drug on the liver. As the clinical response to the drug did not correlate with the cortisol metabolic changes, its therapeutic effect was probably not mediated by its effects on cortisol metabolism.

The 24-hr mean plasma concentrations of 13 hormones or hormone metabolites (cortisol, testosterone, dihydrotestosterone, dehydroisoandrosterone, dehydroisoandrosterone sulfate, androsterone, androsterone sulfate, estrone, thyroxine, triiodothyronine, LH, FSH, and prolactin) were measured in 16 rigorously screened patients (aged 55-80) with stage C or D prostate cancer and 36 normal men. Nine of the hormones showed no abnormalities in the patients but four (testosterone, dihydrotestosterone, cortisol, and estrone) showed abnormalities. Testosterone and dihydrotestosterone, which, respectively, decreased with age and showed no change with age in the normal men, rose sharply with age in the patients. The patients' curves crossed the normal curves at about age 65; patients 65 or above showed normal values while patients under age 65 showed significantly subnormal levels of both hormones: testosterone averaged 282 ng/dl in patients vs 434 ng/dl in controls (P less than 0.0001) and dihydrotestosterone averaged 70 ng/dl in patients vs 99 ng/dl in controls (P less than 0.01). Cortisol, which was age invariant in the normal men, fell sharply with age in the patients; patients under 65 had significantly elevated levels (10.1 vs 6.9 micrograms/dl; P less than 0.0001), while patients 65 or older had normal levels. Estrone levels were age invariant in both patients and controls, but the mean level in patients was markedly elevated (81 vs 47 pg/ml in controls; P less than 0.001). The cortisol/testosterone ratio almost completely separated prostate cancer patients under 65 from normal men, but did not discriminate patients 65 or older from normal. The findings indicate that prostate cancer patients under 65 differ markedly in their endogenous hormonal pattern from patients 65 or older. This leads us to propose a "two-disease" theory of prostate cancer, with possible differences in genetic factors and prognosis.

On the basis of clinical observations suggesting interactive effects of biliary obstruction and estrogen therapy on plasma cholesterol levels, a prospective study of the effect of ethinyl estradiol on plasma lipid levels was carried out in a patient with total biliary obstruction. A daily dose of 50 micrograms of ethinyl estradiol raised the plasma free cholesterol concentration from 265 mg/dl to 550 mg/dl over a period o 3 weeks; there was no change in plasma ester cholesterol concentration. Withdrawal of the estrogen was followed by a fall to baseline of the free cholesterol concentration over a 45-day period; once again there was no change in ester cholesterol. Plasma phospholipid concentration rose and fell in direct proportion to the changes in free cholesterol; plasma triglyceride concentration was unaffected by the estrogen. To account for the results of this study, it is suggested that the already elevated plasma levels of lipoprotein-X in biliary obstruction are further elevated by estrogen administration.

Plasma luteinizing hormone (LH) and testosterone (T) were measured by radioimmunoassay in 9 pubertal boys and 9 sexually mature adult men at 20 min intervals for 24 h. Polygraphic monitoring of sleep was also carried out to precisely identify sleep onset, wakefulness and specific sleep stages. In all 9 pubertal boys, plasma LH showed the characteristic augmentation of secretion synchronous with sleep. This increased LH secretory activity was effective in stimulating increased T secretion during sleep that resulted in uniformly higher mean T concentrations during sleep compared with waking. Plasma LH and T were also measured in 3 of these pubertal boys during acute inversion of the sleep wake cycle. The results showed that plasma LH and T were now augmented during the reversed daytime sleep period; the mean LH and T concentrations were significantly higher than during nocturnal waking. Measurement of LH and T in the 9 adult men showed episodic secretion of both hormones during waking and sleep periods with no consistent augmentation of either hormone during sleep.

Three children with hypothalamic tumors were found to have varying degrees of anterior and posterior pituitary insufficiency. Two had undetectable plasma levels of immunoreactive growth hormone (less than 1 ng/ml) and one had levels within the normal fasting range (1–4 ng/ml). None responded to any stimulus with a rise in plasma immunoreactive growth hormone. In spite of this, all patients showed normal or accelerated linear growth and markedly excessive weight gain. Sulfation factor activity (somatomedin) was detectable in the serum of all three patients. This indicates that some substance other than immunoreactive growth hormone, capable of producing growth and stimulating formation of sulfation factor is being produced in these children and is responsible for this syndrome.

Summary Utilizing a glucose oxidase analytical method, free glucose has been found to be virtually absent from human bile, both in the normoglycemic state and during induced hyperglycemia. In contrast, orally administered xylose appears in bile in concentrations similar to those of plasma. These results suggest a physiologically determined blood-bile barrier for glucose in man. Possible mechanisms for this phenomenon are discussed.

Coprostanol-C14, biosynthetically prepared, was administered orally to two patients, and cholestanol-4-C14 was administered to one of them 10 months later. At the time when radioactivity in the circulation was at a maximum, 3.6 and 3.5% of the administered labeled coprostanol was present in the plasma; the corresponding value after administration of cholestanol-C14 was 4.7%. The dynamic behavior of absorbed radioactive cholestanol was identical with that of orally ingested cholesterol-4-C14, including the esterification process; on the other hand, virtually no coprostanol ester was present in the circulation. It is suggested that the conformation of the A/B rings or configuration at C-3 are related to the esterification mechanism of sterols. After 5 days, over 50% of both compounds had been excreted in the feces. The conversion of coprostanol-C14 to coprostanone-C14 has been demonstrated.

Individual metabolites of steroid hormones were isolated and measured from the urine of patients with chronic myelogenous leukemia. The results were compared with earlier studies of patients with chronic lymphatic leukemia, men with prostatic cancer, women with breast cancer and normal men and women. The metabolites of hydrocortisone were in the normal range for the patients with chronic myelogenous leukemia but the amount of tetrahydrocortisol was generally greater than that of tetrahydrocortisone. There was no evidence for a sex difference in the production of these metabolites. The tentative conclusion was drawn that metabolites of the "adrenal androgens" were also in the normal range in chronic myelogenous leukemia. These results contrast with those in chronic lymphatic leukemia patients where a sex difference in production of hydrocortisone was evident and the metabolites of "adrenal androgens" were at low levels in both sexes.

The specific activities of tetrahydrocortisone and tetrahydrocortisol were measured in a selected series of patients by at least 3 methods, including double isotope derivative analysis. By the method of double isotope derivative analysis with carrier addition and fractional recrystallization to constant isotope ratio the specific activity of the 2 metabolites differed by 20–60% in some of the subjects. Where a difference existed between the 2 estimates the specific activity of tetrahydrocortisone was invariably higher than that of tetrahydrocortisol. These facts establish that at least one of these values will give a false estimate of production rate and leave the validity of the remaining value in serious doubt.

To evaluate the secretory patterns of luteinizing and follicle-stimulating hormones in various forms of sexual precocity, plasma levels of these hormones were measured every 20 minutes for 24 hours in six patients and nine normal pubertal children. Three patients with "idiopathic" precocious puberty and one boy with a hypothalamic tumo rand precocious puberty exhibited fluctuating plasma concentrations that resembled findings in normal pubertal children in that they had significantly increased luteinizing hormone concentrations during sleep. Two boys with congenital adrenal hyperplasia and advanced bone age also showed episodic fluctuation of both hormones and augmented luteinizing hormone concentrations during sleep. These findings show that patients with precocious puberty related either to Central-nervous-system stimulation or to a primary adrenal disorder can exhibit the normal pubertal luteinizing hormone pattern of augmented secretory activity synchronous with sleep. (N Engl J Med 289:282–2...

Endocrine hormones were found to mediate the rapid leukocyte repopulation of peripheral blood that occurs within 6 hr of an intraperitoneal injection of cortisol. The thymus and lymph nodes both participate in the proliferative response; the degree of leukopenia and the rate of leukocyte repopulation were both decreased after removal of thymus or lymph nodes. Splenectomy, however, did not alter the rate of leukoycte repopulation. The leukocyte count decreased more rapidly in adrenal—demedullated than in intact or adrenalectomized rats, but the time course of leukocyte repopulation was the same in each group. Hypophysectomy, but not thyroidectomy, prevented leukocyte repopulation within the 6–hr period. 3H—thymidine incorporation into DNA of lymph nodes and thymus, but not spleen, was significantly less in hypophysectomized than intact rats. Evidence for an increased concentration of a hormone that promotes leukocytic proliferation was found in plasma of intact cortisol—treated rats; the uptake of 3H—thymi...

The metabolic transformation of 11α-hydroxy-Δ4-androstene-3,17-dione has been studied in 2 subjects, a normal man and a hypothyroid patient. It was found that the metabolic transformation was slow and incomplete. The 11α-hydroxyl group was not readily oxidized; none of the metabolites of adrenosterone was isolated. It was demonstrated that conjugation of the 11α-hydroxyl group of the administered steroid with glucuronic acid can occur. The only metabolic product isolated and characterized in both studies was 3α,11α-dihydroxy-50-androstan-17-one; its 5β-epimer could not be detected. 3-Hydroxy-Δ4-allylic steroids, which are the principal metabolites of 11β-hydroxy-Δ4-androstene-3,17-dione in hypothyroid subjects, were not present in detectable amounts.

Plasma luteinizing hormone (LH) was measured by radioimmunoassay at 20-min intervals for 24-hr in 5 normal men before and after the daily administration of 100 mg clomiphene citrate for 7 days. The results showed that clomiphene caused a significant (P < 0.001) increase in the 24-hr mean LH concentration in all 5 subjects. The range of the percent increase was 135–245 with a mean of 180%. In spite of the highly significant increase in the 24-hr mean LH concentration there were instances of overlap of isolated LH values in the control and clomiphene studies. Analysis of the 24-hr plasma curves showed that the increased mean LH concentration was achieved by either increasing the amount of LH secreted per secretory episode or the number of major secretory episodes or both. Calculation of the LH production rate from the 24-hr LH secretory patterns showed a mean percent increase of 189% with a range of 149–259. Estimation of the LH “half-life” from the declining phase of the secretory episodes showed a cluster...

The influence of age and sex on normal estradiol metabolism has been studied by administration of tracer amounts of 3H-estradiol iv to 7 normal young women (aged 22–33), 6 normal young men (aged 23–25), 5 normal elderly women (aged 50–80) and 5 normal elderly men (aged 58–77). It was found that the young women, but not the elderly women, showed substantially increased urinary recovery of radioactivity in the first 24 hr after administration of the tracer compared to the combined male group (44 vs. 28% of the dose, p

A procedure for the isolation of acids from defatted ethanolic extracts of human feces has been described which involves chromatography of their crude methyl ester acetates on silica gel. 10-Hydroxystearic acid, lithocholic acid, and deoxycholic acid have been shown to be the principal constituents of the alcohol-soluble acid fraction. It has been shown that the specific activity of deoxycholic acid in the feces is approximately equal to that of plasma ester cholesterol by the ninth day after the administration of cholesterol-4-C 14 to patients. A method has been presented which permits calculation of the fecal excretion of bile acids after the administration of a tracer dose of cholesterol-4-C 14 . This requires measurement of the total radioactivity in the stool acid fraction and determination of the specific activity of plasma cholesterol; by this method, an average excretion of 290 mg./day of bile acids has been found for the patients studied.

Plasma samples were collected every twenty minutes from each of five normal women and luteinizing hormone was measured by radio-immunoassay. Plasma concentrations of luteinizing hormone were decreased in the first part of the sleep period with the maximum drop occuring during the third hour following stage II onset. Analysis of similar data from a group of five normal men revealed no significant differences in the LH secretory pattern between waking activity and sleep or between the two halves of the sleep period. Analogy was made with the differential capacity of the hypothalamus in males and females to release LH cyclically. Speculation was offered on the possible role of the pineal gland in the sleep-related changes of LH secretion in women.

Tetrahydrocortisol (THF) metabolism was studied by I.V. administration of trace amounts of 3H-THF to 3 normal men and 4 patients with miscellaneous illnesses. The principal urinary steroid was THF. This constituted about half of the “glucosiduronates” in the normal subjects, but significantly more (61–79%) in 3 of the 4 patients. Reduction of the 20-ketone of THF was quantitatively less prominent than the corresponding reaction for THE, but similarly stereoselective. Total cortols constituted 2–12% of the “glucosiduronates”, and the 111β-epimer predominated by about 15:1. The major conversion product of THF was 11β-hydroxyetiocholanolone, 12–25% of the “glucosiduronates” in normal subjects. Three of the four patients showed significantly diminished formation of this metabolite (3–5% of the “gluco-siduronate”). This suggests that diminished side-chain removal of THF may occur non-specifically in ill subjects. In one of these 3 patients, the low 11β-hydroxy-etiocholanolone formation was associated with extremely high β-cortol formation (32% of the “glucosiduronate” suggesting that β-cortol serves as one of the immediate precursors of 11β-hydroxyetiocholanolone.

Cortisol labeled at C-4 with 14C and in the α-position at C-11 with 3H was given iv to 3 subjects. Blood samples were obtained from arm vein, radial artery and renal vein at short time intervals. These were analyzed for cortisol, cortisone and tritiated water. Urine samples at frequent intervals were analyzed for cortisol, cortisone and tritiated water. The biological half-lives of the 14C and 3H species of cortisol, were, respectively, 60–75 and 30–45 min. The difference is the result of reduction of cortisone to cortisol. 3H appeared rapidly in water and approximately 50% of the injected label was in the body water at the end of 2 hr. Measurements of the renal V-A differences in tritium water content indicated that about 10% of the 3H that eventually entered body water was the result of oxidation of cortisol by kidney 11α-hydroxysteroid dehydrogenase. The isotope ratio 3H/14C of plasma cortisol was greater than that injected during the early samples, indicative of a large primary isotope effect...

The pattern of steroid hormone metabolites was examined in a group of patients with chronic lymphatic leukemia. Both men and women produced more tetrahydrocortisol than tetrahydrocortisone. The men showed a lower than normal production of metabolites of hydrocortisone2; the women had an approximately normal amount of these products. Both sexes showed a relatively low level of androsterone and etiocholanolone. The findings are not considered specific for the disease but, rather, indicate the direction for further study.

The concentration of labeled progesterone in the mammary glands 40–45 min after administration of the tracer was 10 times the concentration in vena cava plasma. The concentration of progesterone-4-14C in plasma of the mammary veins was higher than that in the vena cava, indicating that the half-life of progesterone was longer in mammary tissue than that in the general circulation. The concentration of labeled 20α-hydroxypregn-4-en-3-one as a fraction of the concentration of progesterone-4-14C was 1/4 in vena cava plasma, 1/2 in mammary tissue and 5/7 in mammary vein plasma, indicating that conversion of progesterone to 20α-hydroxypregn-4-en-3-one facilitates its release from the gland. The presence of a high level of 20α-hydroxysteroid dehydrogenase activity in mammary tissue was demonstrated in vitro. The limited conversion of 20α-hydroxypregn-4-en-3-one to further products in vitro was supported by the in vivo data. 3β-Hydroxy-5α-pregnan-20-one was found to be specifically absorbed from plasma rather th...

The in vivo transformation of 3β, 17-dihydroxy-Δ5-pregnene-20-one-7α-H3 was studied in 2 patients before and during administration of 2,2-bis[2-chlorophenyl-4-chlorophenyl]1,1-dichloroethane (o,p′-DDD). The drug diminished biotransformation to pregnane-3α-17,20α-triol, while the formation of Δ5-pregnene-3β,17,20α-triol was unchanged. These results, together with an earlier report, establish that o,p′-DDD, in addition to suppressing adrenocortical secretion, acts as an inhibitor of the enzyme systems responsible for transformation of a 3β-hydroxy-Δ5-steroid to its 3α-hydroxypregnane analog. The inhibition is probably directed toward a 3β-hydroxy-Δ5-steroid dehydrogenase.

The metabolic disposition of androsterone-3-3H,4-14C in 2 subjects has been studied. Dehydrogenation of the C-3 hydroxyl group with resynthesis of androsterone was quite extensive. Part of the androsterone that was retained in the body for a longer term lost as much as 80% of the isotope initially at C-3. Much of this tritium appeared promptly in the body water and the isotope continued to accumulate throughout the study. Recovery of the carbon skeleton was less complete and virtually all the 14C was present as androsterone. Elimination was almost exclusively by way of the urine; feces contained only small amounts of the administered 14C. Declining 3H/14C ratio of androsterone with time suggested a continuous process of oxidation of the 3α-hydroxyl group and resynthesis by reduction with protium. There was a difference in isotope ratio between androsterone conjugated as “glucosiduronate” and “sulfate.” The study demonstrates the surprising extent to which an important biologically active hormone ...