STEROID METABOLISM IN VITRO BY AN INTERSTITIAL CELL TUMOUR AND THE ATTACHED PREPUBERTAL TESTIS

1973 ◽  
Vol 59 (3) ◽  
pp. 637-649 ◽  
Author(s):  
GWEN RICHARDS ◽  
A. MUNRO NEVILLE
Keyword(s):  
Metabolic Pathways ◽  
Interstitial Cell ◽  
Reductase Activity ◽  
Testicular Tissue ◽  
Cell Tumour ◽  
Tumour Tissue ◽  
Steroid Metabolism

SUMMARY A virilizing interstitial cell tumour and the attached testicular tissue from a 4-year-old boy were incubated in vitro with [7α-3H]pregnenolone and [4-14C]progesterone, or [4-14C]androstenedione and [7α-3H]5α-dihydrotestosterone. Ring A saturated steroids were produced from 4-ene precursors by the prepubertal testis, but this tissue was unable to convert pregnenolone or progesterone to 17α-hydroxylated C21 steroids, or to C19 steroids. The virilizing interstitial cell tumour metabolized pregnenolone and progesterone to 17α-hydroxyprogesterone, androstenedione and testosterone. In addition, dehydroepiandrosterone was detected as a product of pregnenolone. The tumour lacked 4-ene-5α-steroid reductase activity. 5α-Dihydrotestosterone was metabolized to 5α-androstane-3,17-dione, androsterone, isoandrosterone, 5a-androstane-3α,17β-diol and 5α-androstane-3β,17β-diol in both the normal and tumour tissue. The significance of these metabolic pathways is discussed.

STEROID METABOLISM OF A SERTOLI CELL TUMOUR OF THE TESTIS OF A DOG WITH FEMINIZATION AND ALOPECIA AND OF THE NORMAL CANINE TESTIS

1967 ◽  
Vol 38 (1) ◽  
pp. 61-NP ◽  
Author(s):  
C. G. PIERREPOINT ◽  
JEAN McI. GALLEY ◽  
K. GRIFFITHS ◽  
J. K. GRANT
Keyword(s):  
Sertoli Cell ◽  
Direct Evidence ◽  
Hydroxysteroid Dehydrogenase ◽  
Testicular Tissue ◽  
Cell Tumour ◽  
Tumour Tissue ◽  
Steroid Metabolism ◽  
Enzyme Systems ◽  
Sertoli Cell Tumour

SUMMARY The metabolism of [7α-3H]pregnenolone and [4-14C]dehydroepiandrosterone (DHA) by a Sertoli cell tumour of the testis from a dog with signs of feminization has been studied in vitro and compared with the metabolism of the normal canine testis. The tumour formed oestrone and oestradiol-17β from DHA thus providing direct evidence for the synthesis of oestrogen by this type of neoplasm. Relative or complete inactivity of several enzyme systems involved in the synthesis of testosterone was found in the tumour tissue, and the conversion of either precursor to testosterone was considerably less than in the normal testis. Suggestive evidence is presented for the occurrence of steroid-specific 17α-hydroxylase and 3β-hydroxysteroid dehydrogenase-isomerase systems in canine testicular tissue. The formation of sulphates of pregnenolone and DHA was shown both in normal and in neoplastic tissues and, in addition, the tumour either formed the sulphate of 17α-hydroxypregnenolone or caused the 17α-hydroxylation of pregnenolone sulphate.

A COMPARATIVE STUDY OF THE BIOSYNTHESIS OF TESTOSTERONE BY HUMAN TESTES AND A VIRILIZING INTERSTITIAL CELL TUMOUR

1967 ◽  
Vol 56 (4) ◽  
pp. 726-736 ◽  
Author(s):  
D. C. Sharma ◽  
E. A. Racz ◽  
R. I. Dorfman ◽  
E. J. Schoen
Keyword(s):  
Interstitial Cell ◽  
Testicular Tissue ◽  
Cell Tumour ◽  
Isotopic Dilution ◽  
Testicular Tumour ◽  
Early Puberty ◽  
Laboratory Findings ◽  
Major Reaction ◽  
The Right

ABSTRACT A comparative in vitro study of an interstitial cell tumour of the testis from a virilized patient and »normal« testes from another male has been made by incubating homogenates of these tissues with radioactive progesterone, 17α-hydroxyprogesterone, testosterone and androst-4-ene-3,17-dione-4-14C. The patient with the testicular tumour was a 14-year old boy whose clinical studies, reported in detail elsewhere, revealed a history of early puberty and laboratory findings of markedly elevated levels of urinary total 17-ketosteroids and pregnanetriol. These urinary values fell to normal following removal of the right testicular tumour, which was interpreted as being a benign interstitial cell tumour on histologic examination. The radioactive metabolites from the testicular tissue of both subjects were separated, purified and identified by partition column chromatography in various systems with authentic standards, formation of derivatives and isotopic dilution analysis. The interstitial cell tumour converted a significant amount of the substrate progesterone into 16α-hydroyprogesterone, besides testosterone and androst-4-ene-3,17-dione; reduction at C20 was also a major reaction when either progesterone or 17α-hydroxyprogesterone was the substrate. On a comparative basis the activity of C17-20 desmolase was about five times more in the tumour as compared to the testicular tissue.

STEROID METABOLISM BY AN OESTROGEN-DEPENDENT INTERSTITIAL-CELL TUMOUR OF A RAT TESTIS

1973 ◽  
Vol 59 (1) ◽  
pp. 7-16
Author(s):  
J. W. JULL ◽  
D. McCLELLAN ◽  
S. COUPEY
Keyword(s):  
Interstitial Cell ◽  
Cell Tumour ◽  
Steroid Metabolism ◽  
Rat Testis

SUMMARY Steroid metabolism by a unique, transplantable, oestrogen-induced, hormone-dependent interstitial-cell tumour of a rat testis was investigated. After incubation of the minced tumour in medium without substrate the presence of 3α-androstanediol, 3-epiandrosterone and androsterone was shown. There was inconclusive evidence for the presence of smaller amounts of 3β-androstanediol, and no evidence for testosterone. [14C]Pregnenolone substrate was shown to be metabolized after 2 h to androstenedione, androsterone and a small amount of testosterone. Epi- and dehydroepiandrosterone were probably formed from [14C]pregnenolone, but were incompletely characterized.

17-ketosteroid reductase deficiency — plasma steroids and incubation studies with testicular tissue

1980 ◽  
Vol 94 (3) ◽  
pp. 397-403 ◽  
Author(s):  
K. v. Schnakenburg ◽  
F. Bidlingmaier ◽  
D. Engelhardt ◽  
O. Butenandt ◽  
P. Unterburger ◽  
...  
Keyword(s):  
Reductase Activity ◽  
Testicular Tissue ◽  
Breast Development ◽  
Tissue Slices ◽  
Reductase Deficiency ◽  
Sex Assignment ◽  
Stimulation Tests ◽  
Plasma Steroids ◽  
Testicular Feminisation

Abstract. The patient, diagnosed as a case of testicular feminisation in infancy, was examined at the age of 15 years because of severe symptoms of virilising puberty with poor breast development. Plasma steroid analyses revealed a 10-fold elevated androstenedione concentration (A: 1562 ng/100 ml). Testosterone (T: 266 ng/100 ml) was in the male pubertal range. Thus the A/T-ratio was far above normal. The oestrone/oestradiol ratio was also elevated (Oe1/Oe2: 10.2/2.2 ng/100 ml). A, T, Oe1 and Oe2 could not be suppressed by dexamethasone, but reacted promptly to fluoxymesterone (A: 781 ng/100 ml). hCG caused a further increase of the A/T-ratio (2220/246 ng/100 ml); ACTH did not alter the A-concentration. These findings together with simular investigations after gonadectomy suggest that the failure to convert A to T and Oe1 to Oe2 is essentially located in the testes. In vitro incubations of testicular tissue showed reduced 17-ketosteroid reductase activity in tissue slices and in the subcellular fractions microsomes and cytosole. This form of male pseudohermaphroditism can easily be detected already in infancy, if steroid analyses and stimulation tests are performed. In case of female sex assignment patients should be submitted to early orchidectomy in order to avoid virilisation in puberty.

Effects of gonadal steroid hormones on the hypothalamo-pituitary-liver axis in the control of sex differences in hepatic steroid metabolism in the rat

1982 ◽  
Vol 95 (2) ◽  
pp. 181-187 ◽  
Author(s):  
Agneta Mode ◽  
Gunnar Norstedt
Keyword(s):  
Subcutaneous Injection ◽  
Reductase Activity ◽  
Gonadal Hormones ◽  
Anterior Hypothalamus ◽  
Female Rats ◽  
Steroid Metabolism ◽  
Male And Female Rats ◽  
Site Of Action ◽  
Hypothalamic Pituitary Axis

The site of action of gonadal hormones in the regulation of hepatic steroid metabolism was investigated by measuring the effects of (i) implantation of oestradiol into the pituitary gland or anterior hypothalamus of males and (ii) subcutaneous injection of a synthetic androgen in deafferentated male and female rats. The hepatic responses measured in vitro were 5α-reduction, and 6β- and 16α-hydroxylation of androstenedione. After intrapituitary or intrahypothalamic implantation of oestradiol, 5α-reductase activity increased and 6β- and 16α-hydroxylase activity decreased in males relative to the enzyme activities of cholesterol-implanted animals, indicating a feminizing effect of the oestrogen. This effect could not be accomplished by subcutaneous injection of the same oestrogen preparation. Deafferentation had no effect on hepatic steroid metabolism in females, but caused a feminization in males. In addition, subcutaneous treatment of intact females with the synthetic androgen caused masculinization of hepatic steroid metabolism, but was without effect in deafferentated animals. Treatment with synthetic androgens had no effect on the hepatic steroid metabolism in deafferentated male animals. Subcutaneous injection of a potent synthetic progestagen had little effect on hepatic steroid metabolism in intact females. It is concluded that oestrogen feminizes hepatic steroid metabolism by an action at the hypothalamic-pituitary level and that an intact hypothalamic-pituitary axis is required for the masculinizing action of the synthetic androgen on hepatic steroid metabolism. It is possible that the site of action of androgens is in the anterior hypothalamus or in adjacent areas of the brain.

METABOLISM OF [7α-3H]DEHYDROEPIANDROSTERONE AND [4-14C]ANDROSTENEDIONE IN VITRO BY TESTICULAR TISSUE FROM ADULT AND PREPUBERTAL WISTAR RATS

1974 ◽  
Vol 63 (1) ◽  
pp. 149-155 ◽  
Author(s):  
GWEN RICHARDS ◽  
A. MUNRO NEVILLE
Keyword(s):  
Wistar Rats ◽  
Reductase Activity ◽  
Testicular Tissue ◽  
Adult Rat

SUMMARY The metabolism of [7α-3H]dehydroepiandrosterone (DHA) and [4-14C] androstenedione in vitro was investigated in 30-day-old (prepubertal) and adult rat testicular tissue in the presence of cyanoketosteroid, a 5-ene-3β-hydroxysteroid oxidoreductase inhibitor. Whereas both substrates were converted to 5α-reduced steroids by the prepubertal testis, 4-ene-steroid-5α-reductase activity was negligible in the adult gland. Cyanoketosteroid prevented the formation of 5α-reduced steroids from DHA by the prepubertal testis indicating testosterone and androstenedione as intermediates in their production.

Feminising Interstitial Cell Tumour of the Testis

1973 ◽  
Vol 59 (2) ◽  
pp. 71-76
Author(s):  
S. P. Gray ◽  
H. Chandler ◽  
K. C. Bouskill ◽  
N. J. Blacklock
Keyword(s):  
Negative Feedback ◽  
Normal Level ◽  
Interstitial Cell ◽  
Testicular Tissue ◽  
Feedback Mechanism ◽  
Cell Tumour ◽  
Negative Feedback Mechanism ◽  
Normal Limits ◽  
Androgenic Steroids ◽  
Stimulation Of

AbstractA case of an interstitial cell tumour of the testis associated with bilateral gynae-comastia is described. The patient excreted excessive amounts of oestrogen in the urine whilst the 17-oxosteroids were within normal limits. Analysis of the testicular tumour removed at operation showed that it contained much more oestrone, andros-terone, dehydroepiandrosterone (DHEA), and aetiocholanolone, than did the non neoplastic testicular tissue surrounding the tumour.It is suggested that these steroids produced by the tumour were the cause of the patient’s feminisation, and that there were two effects reinforcing each other, viz, the excess of oestrogen itself and the presence of sufficient amounts of weakly androgenic steroids to lower the normal level of testosterone production by the testis.These effects could have been mediated in two different ways; indirectly by stimulation of the negative feedback mechanism of the pituitary causing less ICSH to reach the testis, and directly by the inhibition of the enzymes concerned with the normal biosynthesis of testosterone in the testis.

HORMONAL STUDIES OF A BENIGN INTERSTITIAL CELL TUMOUR OF THE TESTIS PRODUCING ANDROSTENEDIONE AND TESTOSTERONE

1967 ◽  
Vol 56 (3) ◽  
pp. 481-489 ◽  
Author(s):  
Laurence C. Wegienka ◽  
Felix O. Kolb
Keyword(s):  
Interstitial Cell ◽  
Cell Tumour ◽  
Primitive Cell ◽  
Cell Type ◽  
Urinary Steroids ◽  
Metabolic Products ◽  
Adrenal Rest ◽  
Slow Growing ◽  
Dexamethasone Suppression

ABSTRACT A case is described of a 14-year old male who presented with precocious puberty resulting from a benign slow growing interstitial cell tumour of the testis. Preoperative studies revealed a marked increase in urinary 17-ketosteroids, pregnanetriol and testosterone glucuronide. The urinary steroids showed little change following corticotrophin stimulation, dexamethasone suppression or chorionic gonadotrophin stimulation demonstrating the autonomous nature of this tumour. Although the urinary testosterone glucuronide levels were markedly elevated, the plasma levels of testosterone were normal and androstenedione elevated. These findings are in accord with in vitro findings of this tumour and support the premise that one of the primary metabolic products of this tumour was androstenedione which was peripherally transformed to testosterone glucuronide which was then excreted in the urine. The elevated 17-hydroxycorticosteroids and pregnanetriol, which returned to normal following removal of the tumour, together with the absence of any crystalloids of Reinke, suggest that the tumour may be of a biologically primitive cell type or of adrenal rest origin.

Sign in / Sign up

Export Citation Format

Share Document