Testosterone Production Rates in Normal Adults

Abstract

The investigation of clinical and physiological problems related to androgen production has been hampered by lack of an adequate measure of testosterone production. As one approach to this problem, Finkelstein, Forchielli, and Dorfman (1) developed a sensitive method for the measurement of free testosterone in plasma. The subsequent identification of testosterone in the urine (2) as the glucuronoside (3) provided a unique metabolite for the estimation of testosterone production rate by the isotope-dilution method. One such study, using an isotope-derivative method to quantitate testosterone, was briefly reported by Hudson, Coghlan, Dulmanis, and Ekkel (4).We have measured urinary testosterone by an adaptation of the fluorescence reaction described by Wilson (5). This has facilitated the use of the isotope-dilution method for the measurement of testosterone production rates in man. MATERIALS AND METHODSL.S., L.M., G.S., R.S., J.S., C.Z., and M.G. were healthy young adult volunteers C.S. was a 27-year-old white woman in complete remission after treatment for metastatic choriocarcinoma. Regular menses had occurred for the 6 months before study. E.H. was a 27-year-o'dNegro woman with normal menstrual function admitted for treatment of local recurrence of carcinoma of the breast.Absolute ethanol 1 was redistilled by the method of Peterson and his associates (6). Water was glass-distilled after the addition of a few crystals of KMnO4. n-Hexane, ether, chloroform, and methanol were prepared as previously described (7,8 Silica gel G 4 was washed twice with absolute ethanol and once with redistilled ethanol. After the third wash, the wet powder was heated overnight in an oven at 1000 C and then stored at room temperature in a desic-cator. An alcohol eluate of a 10-g sample of the powder should give no colored residue.The steroids 5 used were obtained from commercial sources. Testosterone and testosterone acetate were recrystallized, and the melting points agreed with reported values. Other materials used were human folliclestimulating hormone (FSH) (potency, 0.1 ml = 1 U NIH FSH-S1) contaminated with a small amount of luteinizing hormone, human chorionic gonadotropin (HCG) ,6 and testosterone-4-C 7 (77 ,&c per mg), which was chromatographed in systems A2 and B6 before use.Partition column chromatography. The technique previously described (7) was modified so that extracts of 1.5 days' urine could be resolved on a single column.The glass tube was 48 mm i.d. and 30 mm long with a 55: 50 outer joint at the top. Solvent systems are shown in Table I. Seventy g of silica-alumina catalyst, used as supplied, was mixed with 43 ml stationary phase A and packed in about 140 ml mobile phase A previously poured into the column. The dried urine extract was applied with successive portions of 1.2, 0.6, and 0.3 ml stationary phase A, each mixed with an equal volume of mobile phase A. Each transfer was preceded by placing layers of 2, 1, and 0.5 g dry silicate on the column. To develop the column, the successive solvents were allowed to ...

Population Pharmacokinetic/Pharmacodynamic Modeling of Depot Testosterone Cypionate in Healthy Male Subjects

“…The mean post hoc endogenous testosterone secretion rate at baseline in PK models for tT models was 12.5 mg/day. It is suggested that men produce between 4 and 11.8 mg of testosterone per day,23 which is slightly lower than our model estimate. However, there is wide variability in normal testosterone concentrations with ranges reported between 300 and 1,000 ng/dl,24 our model estimates of endogenous testosterone secretion rate are consistent with reported values and close to reported physiological values.…”

Bilirubin Metabolism in Congenital Nonhemolytic Jaundice

“…Urinary "glucuronides" were hydrolyzed with /3-glucuronidase, and the liberated steroids were extracted with ether [21]. Urinary "sulfates" were hydrolyzed by solvolysis and extracted [21].…”

“…Urinary "glucuronides" were hydrolyzed with /3-glucuronidase, and the liberated steroids were extracted with ether [21]. Urinary "sulfates" were hydrolyzed by solvolysis and extracted [21]. Both extracts were counted, and then testosterone was isolated by thin layer chromatography and derivative formation [21].…”

“…Urinary "sulfates" were hydrolyzed by solvolysis and extracted [21]. Both extracts were counted, and then testosterone was isolated by thin layer chromatography and derivative formation [21]. Testosterone- 14 C was used to correct for procedural losses.…”

Excretion and Production of Testosterone in Normal Children, in Children with Congenital Adrenal Hyperplasia, and in Children with Precocious Puberty

“…Just as with other hormones such as hydrocortisone and aldosterone, the production rate of testosterone is determined from the cumulative specific activity of a urinary metabolite, i. e., testosterone glucuronide [16]. This urinary production rate (UPR) is approximately 7 mg/24 h for males and 1-2.5 mg/24 h for females [14,16,24,39]. For normal prepubertal children, only a few data are available.…”