Steroid-secreting tumors of the testis have generally been considered to be of Leydig cell origin. Testicular tumors in patients with congenital adrenal hyperplasia have been thought to be adrenal rests, but no conclusive evidence supporting the hypothesis has been presented. We report a morphological and biochemical analysis of a patient with 21-hydroxylase deficiency who developed bilateral nodular hyperplasia of steroid-secreting tissue within the testis, despite suppression therapy with both exogenous glucocorticoids and testosterone. The tissue was formed of confluent nodules of homogenous cells. Electron microscopy showed the cells to have abundant smooth endoplasmic reticulum, well developed Golgi apparatus, and mitochondria with predominantly tubular cristae, features characteristic of steroid-secreting cells of adrenocortical origin. Crystals of Reinke were not observed. Functional studies in vivo showed a marked response to ACTH infusion, with 17-hydroxyprogesterone rising from 56 to 13,500 ng/mL, cortisol from less than 2 to 19 micrograms/dL, and testosterone from 369 to 629 ng/dL, with an attendant increase in testicular size and pain over 48 h. Receptor studies in vitro revealed no gonadotropin receptors, but abundant angiotensin-II receptors. Enzyme activity analysis in vitro showed undetectable 21-hydroxylase activity and an enzyme profile consistent with adrenocortical cells rather than Leydig cells. Based on these morphological and biochemical findings, we conclude that the nodular steroidogenic tissue that replaced this patient's testes was of adrenal origin. The study documents for the first time the development of adrenocortical tumors from adrenal rest tissue within the testis.

A B S T R A C T The plasma concentrations of dehydroepiandrosterone, androstenedione, and dehydroepiandrosterone sulfate decrease during the first year of life, remain low during childhood, and then increase during adrenarche. To determine whether alterations in adrenal enzyme activity might explain the changing secretory pattem of the adrenal androgens, we measured human adrenal microsomal 3,8-hydroxysteroid dehydrogenase-isomerase, 17,20-desmolase, 17-hydroxylase, and 21-hydroxylase activities. 12 adrenals from individuals aged 3 mo to 60 yr were studied. The patients were divided into three groups based upon the age of the patient when the adrenal glands were obtained: group 1, infants aged 3-8 mo (n = 3); group 2, preadrenarchal or early adrenarchal children aged 2-9 yr (n = 4); and group 3, adults aged 20-60 yr (n = 5). The mean activity of the 17,20-desmolase, 17-hydroxylase, and 21-hydroxylase fell by 50% and that of 3,8-hydroxysteroid dehydrogenase-isomerase activity rose 80% from group 1 to group 2. A fourfold increase in 17,20-desmolase (P < 0.002) and 17-hydroxylase (P < 0.001) activity and a doubling in 21-hydroxylase activity (P < 0.005) occurred between groups 2 and 3. We conclude that the decline in plasma adrenal androgens after birth appears to be associated with a rise in 3,8-hydroxysteroid dehydrogenase-isomerase and a fall in 17,20-desmolase and 17-hydroxylase activity. The subsequent increase in plasma adrenal androgen concentration during adren-

The neotropical cotton-top marmoset (Saguinus oedipus) is a New World primate known to have markedly increased total and free plasma cortisol concentrations when compared with Old World primates including man. The relative end-organ 'resistance' to glucocorticoids found in various New World primates has been attributed to a glucocorticoid receptor (GR) with diminished affinity for glucocorticoids. It has been demonstrated that the marmoset GR has approximately tenfold lower binding affinity for dexamethasone when compared with the human GR. We have examined the primary structure of the marmoset GR by molecular cloning and sequencing of GR functional domains. A library of cDNA clones was constructed in the phage vector gamma gt10 using poly(A)+ RNA from a marmoset-derived lymphoid cell line, and screened using the human GR cDNA. DNA sequencing determined 76 individual nucleotide substitutions in the coding region of the marmoset GR. Comparison of the marmoset GR nucleotide sequence with the human GR cDNA coding region indicated an overall sequence homology of about 97%. Thirty of the nucleotide substitutions lead to alterations in the predicted amino acid sequence (28 amino acid substitutions) of the marmoset GR. The size of the marmoset GR predicted from the 778 amino acids is approximately 90,000 which is in agreement with previous size estimates of the human and marmoset GRs. Alterations of amino acid sequence in the marmoset GR were greatest towards the amino terminus, including the tau 1 domain putatively involved in transcriptional activation. The DNA-binding domain contained an additional codon (arginine).(ABSTRACT TRUNCATED AT 250 WORDS)

Histologic, hormonal, and enzymatic studies were performed in the rabbit and dog to identify maturational changes similar to human adrenarche. Development of an adrenal reticular zone was observed in both the rabbit and dog, analogous to the change in the man. Plasma dehydroepiandrosterone (DHA) and androstenedione (delta 4-A) increased significantly in postpubertal compared to prepubertal male rabbits and dogs, but the increases were much smaller than those reported in man. Orchiectomy reduced plasma DHA and delta 4-A of adult rabbit and dog to near undetectable levels, suggesting a primarily testicular origin. The activities of adrenal microsomal 17-hydroxylase and 17,20-desmolase in the orchiectomized rabbit and dog were subsequently measured to explain this apparent low adrenal contribution to DHA and delta 4-A. Adrenal 17-hydroxylase activity in the rabbit ad 17,20-desmolase activity in both the rabbit and dog were significantly lower than in an adrenal androgen-secreting primate (cynomolgus macaque). Adrenal 17-hydroxylase activity in the dog, measured 1 wk after castration, doubled after sexual maturation (P less than 0.001). This change was paralleled by a significant rise in basal and ACTH-stimulated plasma 17-hydroxyprogesterone in the intact dog (P less than 0.05). Because adrenal 17-hydroxylase activity has been shown to increase during adrenarche in man, this change may be homologous to human adrenarche.