THE METABOLISM OF TESTOSTERONE, ANDROSTENEDIONE AND OESTRONE BY TESTES FROM A CASE OF TESTICULAR FEMINIZATION

1968 ◽  
Vol 42 (3) ◽  
pp. 391-403 ◽  
Author(s):  
A. P. WADE ◽  
G. S. WILKINSON ◽  
J. C. DAVIS ◽  
T. N. A. JEFFCOATE

SUMMARY [4-14C]Testosterone, [4-14C]androstenedione and [4-14C]oestrone were incubated with testicular tissue obtained from an 18-yr.-old patient with the complete form of the testicular feminization syndrome. Considerable biosynthesis of testosterone from androstenedione occurred, but metabolism of testosterone by the tissue was minimal. The small phenolic fraction from these incubations did not contain any recognizable oestrogens. Metabolism of oestrone was almost complete, less than 4% being recovered as unchanged oestrone. Of eight areas of radioactivity found during chromatography, five were shown to be associated with oestrone, 2-methoxyoestrone, oestradiol-17β, 2-hydroxyoestradiol-17β, and 2-methoxy-oestradiol-17β. Chromatographic evidence suggested that an oxo-oestrone and a compound more polar than oestriol were present. No oestriol was found. The results confirm those of other workers to the effect that testosterone is the major metabolite of androstenedione in feminizing testes. Incubation of the testes with oestrone showed them also to possess the enzyme systems necessary for hydroxylation at position 2 and the subsequent methylation of this group. Urinary steroid measurements before and after removal of the testes showed these organs to be actively secreting. Attempts to demonstrate oestrogenic activity in the urine additional to that accounted for by chemical estimation were unsuccessful.

1980 ◽  
Vol 95 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Martha Medina ◽  
Alfredo Ulloa-Aguirre ◽  
Maria A. Fernández ◽  
Gregorio Pérez-palacios

Abstract. The role of oestrogens on gonadotrophin secretion was assessed in three related patients with the complete form of testicular feminization syndrome. Serum LH and FSH levels were measured before and after I.RH stimulation as well as before, during and after chronic clomiphene citrate administration. Moderately elevated LH basal levels with a significant LH rise following I.RH were observed. Normal or even low FSH level with poor response to LRH were found in all subjects. Administration of clomiphene citrate resulted in a significant serum LH increase without any change of FSH. Following castration both LH and FSH rose and a normal response to LRH was observed. These results were interpreted as demonstrating that, while endogenous oestrogens modulate LH secretion in patients with androgen unresponsiveness, it plays no role in regulating FSH secretion and suggested that a factor of testicular origin without androgenic or oestrogenic activity is responsible for FSH regulation.


1972 ◽  
Vol 50 (8) ◽  
pp. 849-855 ◽  
Author(s):  
C. Cardiff ◽  
V. Uden ◽  
D. W. Killinger

The biosynthesis of sulfate conjugates and unconjugated steroids has been compared in two siblings aged 19 and 21, and a 52-year-old patient with the complete form of testicular feminization. Incubation of homogenates of gonadal tissue with 14C-pregnenolone (P) and 3H-pregnenolone-sulfate (PS) revealed that the conversion of P to PS was 6.8% in the older subject, and less than 1% in the two younger subjects; and the conversion to dehydroepiandrosterone sulfate (DHAS) was 24.2% in the older subject, and 2.1 and 0.2% in the two younger subjects. The recovery of unmetabolized PS was 41.9% in the older subject, and 5.0 and 13.7% in the two younger subjects. The formation of testosterone from P was 4.2 and 2.2% in the two younger subjects, and 0.5% in the older subject, and the 3H/14C ratio indicated that the utilization of PS in testosterone biosynthesis was greater in the younger patients than in the older subject. Incubation of 14C-dehydroepiandro-sterone (D) and 3H-DHAS with testicular tissue from the 21-year-old subject confirmed the high testosterone production and steroid sulfate utilization in the younger subject.These findings raise the possibility that with age there may be a shift from the biosynthesis of biologically active unconjugated products to less biologically active sulfate conjugates in testicular tissue.


1967 ◽  
Vol 38 (1) ◽  
pp. 61-NP ◽  
Author(s):  
C. G. PIERREPOINT ◽  
JEAN McI. GALLEY ◽  
K. GRIFFITHS ◽  
J. K. GRANT

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.


2001 ◽  
Vol 47 (1) ◽  
pp. 30-34
Author(s):  
L. K. Dzeranova ◽  
M. E. Bronstein ◽  
E. I. Marova ◽  
A. V. Vorontsov ◽  
A. A. Pishchulin ◽  
...  

The article is devoted to the study of the complete form of the testicular feminization syndrome with dysherminoma in one testicle combiner with prolactinoma.


1973 ◽  
Vol 73 (1) ◽  
pp. 179-188 ◽  
Author(s):  
R. Sandrini Neto ◽  
M. A. Rivarola ◽  
R. Coco ◽  
C. Bergadá

ABSTRACT Testicular function was studied in 18 patients with abnormalities of sexual differentiation. Fourteen patients were prepubertal and four postpubertal. Plasma testosterone was determined before and after 5000 IU HCG administered daily during 5' days. Of the fourteen prepubertal patients, the two true hermaphrodites and the patient with asymmetrical gonadal differentiation showed a poor response to gonadotrophin stimulation. This could be explained by the small amount of active testicular tissue or its coexistence with ovarian and rudimentary gonadal tissue which might exert some influence on the endocrine function of the testis. In the group of eight patients with male pseudo-hermaphroditism and ambiguous external genitalia, the response to HCG showed a large variation. The three patients with small testes had lowest values i. e. 210, 198 and 192 ng/100 ml. The remaining five patients showed normal values ranging between 360 and 720 ng/100 ml. The ambiguous external genitalia of these patients could be explained as being due to a diminished androgen target organ sensitivity limited to the external genitalia. The three prepubertal patients with male pseudo-hermaphroditism and female external genitalia showed a marked increase in plasma testosterone with HCG ranging between 598 and 1100 ng/100 ml. The four pubertal cases also had high values in basal conditions, between 920 and 1870, which increased even more after gonadotrophin stimulation, in one case from 1382 to 2264 ng/100 ml. This hypersensitivity to exogenous HCG, even in infancy, correlates with the elevated basal values observed in adult patients with otherwise female external genitalia and androgen insensitivity. Finally, the HCG stimulation test could be useful for the demonstration of testicular tissue in prepubertal patient with abnormalities of sexual differentiation, although it cannot be used as a prognosis of masculinization or feminization at puberty.


1979 ◽  
Vol 90 (3) ◽  
pp. 544-551 ◽  
Author(s):  
E. Nieschlag ◽  
E. J. Wickings ◽  
J. Mauss

ABSTRACT In order to detect any possible Leydig cell dysfunction associated with male infertility, the endocrine capacity of the testes was investigated in vivo and in vitro in 21 infertile men. Plasma testosterone was determined before and after 3 days of hCG stimulation. Testicular tissue obtained by bilateral biopsies was subjected to (1) histological examination, (2) determination of basal testosterone concentration and (3) incubation with hCG. Patients were grouped according to histology. In vitro basal and stimulated testicular testosterone was similar in patients with normal histology, Sertoli-cell-only syndrome and spermatogenic arrest. Tissue from patients with Leydig cell hyperplasia showed 3-fold higher basal testosterone levels and a greater response to hCG. All patients had plasma testosterone levels and responses to hCG in the normal range. There was no significant correlation between the data obtained in vivo and in vitro, indicating that testosterone determinations in peripheral blood do not necessarily reflect the intratesticular situation. There was no evidence for gross abnormality in Leydig cell function accompanying disturbed spermatogenesis.


1967 ◽  
Vol 54 (2) ◽  
pp. 193-207 ◽  
Author(s):  
Tohru Uozumi ◽  
Ryoichi Nozaki ◽  
Keishi Matsumoto ◽  
Tokuichiro Seki ◽  
Jun-ichi Furuyama

ABSTRACT A patient, aged 20, with a mosaicism of XO/XY/XXY (23:21:14) in the sex chromosome is described. The clinical picture of the patient was similar to that of the testicular feminization syndrome. The patient had three brothers but no sisters. Maternal history was negative. Although the preoperative urinary 17-ketosteroid excretion was double that of normal male adults, urinary oestrogens were within the normal range of adult males. It was found that the urinary 17-KS especially C19O2-17-KS and oestrogens markedly decreased after removal of the gonads while the urinary 17-hydroxycorticosteroids remained almost unchanged. An in vitro biosynthesis of the steroids was studied with pregnenolone used as a substrate in the testicular tissue from cryptorchid gonads. From the results obtained there is nothing to suggest that this endocrine disorder could be explained by an inability to synthesize testosterone. The formation of oestrogens in vitro was not demonstrated.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Ezzati ◽  
M Pashaiasl

Abstract Study question Could choosing of non-apoptotic spermatozoa by biological biomarkers such as microRNAs promote post-thaw fertilization ability? Summary answer Biological alterations in correlation with apoptosis and oxidative stress markers such as microRNAs may preserve the function and fertility of spermatozoa during cryopreservation. What is known already Biological changes of cryopreserved spermatozoa such as microRNAs against cryo-injury were investigated. It was presented that several sperm parameters such as motility and abstinence period can impact the percentage of post-thaw sperm survival. Recent study, reported that microRNAs related to process of motility, sperm structure and apoptosis were associated with different expression after cryopreservation. More comprehensive study needed to fully mention the effect of microRNAs and their correlations with other biomarkers in cryopreservation. Study design, size, duration Our study was performed on 58 men who were 24–40 years old. Their ejaculated samples were classified as sever (concentrations less than 5 million sperm/mL) Oligoasthenoteratozoospermia (SOAT), mild (concentrations 5 million – 10 million sperm/ mL) Oligoasthenoteratozoospermia (MOAT), obstructive azoospermai (OA), Non obstructive azoospermai (NOA) (absence of spermatozoa in the semen) and normal group (concentrations more than 15 million sperm/ mL). Then each sample was grouped into fresh and cryopreserved one. Participants/materials, setting, methods Density Gradient centrifugation (DGC) was performed to obtain high quality sperm without round cells after freeze-thawing. Biopsy of testicular tissue was prepared after Testicular Sperm Extraction (TESE) surgery. Then biological biomarkers were examined before and after cryopreservation including microRNA–122 (miR–122), miR–383, miR–15b, miR–184, miR–34c and target genes such as P53, Caspase9 and CYCLIN D1, using Quantitative real-time polymerase chain reaction (RT-PCR). Glutathione peroxidase (GPx), Superoxide dismutase (SOD) and malondialdehyde (MDA) using imaging multi-mode reader. Main results and the role of chance There was a significant reduction in sperm total motility and morphology in Cryopreserved-infertile groups (MOAT and SOAT) compared with the Fresh-infertile groups. Decreased level of GPx activity was associated with increased concentration of MDA during freeze-thawing procedure in oligoasthenoteratozoospermia. Also increasing levels of SOD, and DNA fragmentation were showed. Our data demonstrated that reduction of CYCLIN D1 in MOAT-Cryopreserved (P = 0.0174) and NOA-Cryopreserved (P = 0.0001) groups were considerable compared with their fresh ones. We observed high level of Capase9 and in cryopreserved groups (P = 0.01).The expression of miR–34c was increased significantly in NOA-Cryo (P = 0.0064), and OA-Cryo (P = 0.0441) in comparison with their fresh groups. The expression of miR–184 (P = 0.0275) was enhanced in NOA-Cryo as compared to NOA-Fresh. Quantitative RT-PCR demonstrated meaningful decrease level of miR–383 expression in SOAT-Cryopreserved as compared with SOAT-Fresh (P = 0.0223). On the other hand, expression level of miR–383 was increased in NOA group significantly (P = 0.0437) and in OA group non-significantly during freezing. There was non-significant decrease of miR–122 and miR–15b in MOAT and SOAT-Cryopreserved groups in comparison to their Fresh groups. We observed reduced expression of miR–122 (P = 0.0109) and miR–15b (P = 0.0322) in OA group after freezing. Also, there was meaningful increased level of miR–15b (P = 0.0234) in NOA-Cryo compared with Fresh. Limitations, reasons for caution Because of the ethical principle, we can not obtain testicular samples from normal groups. So, we analyzed NO and OA groups with each other. Wider implications of the findings: Our study documented that total motility can be interfered by microRNAs. This phenomenon effects on the total motility of post-thaw spermatozoa. Also the increase level of MDA may disturb microRNAs regulation in the infertile cases. These non-coding RNAs may be known as fertility biomarker to development of freeze-thawing strategies. Trial registration number 60961


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