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

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.

1973 ◽  
Vol 59 (3) ◽  
pp. 637-649 ◽  
Author(s):  
GWEN RICHARDS ◽  
A. MUNRO NEVILLE

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.


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.


1973 ◽  
Vol 59 (2) ◽  
pp. 71-76
Author(s):  
S. P. Gray ◽  
H. Chandler ◽  
K. C. Bouskill ◽  
N. J. Blacklock

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.


1967 ◽  
Vol 56 (3) ◽  
pp. 481-489 ◽  
Author(s):  
Laurence C. Wegienka ◽  
Felix O. Kolb

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.


2012 ◽  
Vol 153 (8) ◽  
pp. 303-307 ◽  
Author(s):  
László Ságodi ◽  
Janka Jakab ◽  
Ákos Kiss ◽  
Erzsébet Ladányi ◽  
Erzsébet Balogh ◽  
...  

The authors report a case of a dysgenetic male pseudohermaphroditism with a 45,X/46,XY karyotype in a mosaic form, which was diagnosed in an infant. The one-week-old infant was evaluated because of proximal hypospadias and retention of the right testis. The results of hormonal tests were the followings: serum FSH 5.2 mU/ml; LH: 2.0 mU/ml; testosterone: 144.3 ng/dl; androstendione: 0.42 µg/l; 17-hydroxyprogesterone: 1.12 ng/ml. Chromosomal analysis revealed 45,X/46,XY karyotype. Fluorescent in vitro hybridization showed that 51% of the lymphocytes had the Y chromosome and the SRY gene. Analysis of the SRY showed no deletion in the AZF a,b,c regions. Pelvic magnetic resonance imaging indicated the presence of vagina between the bladder and the rectum, and it showed a mass measuring 15×8 mm in the right inguinal canal as well as an oval gonadal mass with a size of 13×7 mm in the left scrotum. During surgical intervention, performed at the age of one, the right gonad was removed and biopsy of the scrotal testis was performed. Histological examination revealed dysgenetic testis in both sides. The authors emphasize the necessity of cytogenetic and endocrinological investigations of newborns with perineoscrotal hypospadia and bilateral or unilateral maldescent testes immediately after birth. Surgical removal of the dysgenetic testicular tissue located in the abdominal cavity and its histological evaluation provides separation of mixed gonadal dysgenesis, dysgenetic male pseudohermaphroditism, bilateral gonadal dysgenesis and ovotestis in the 45,X/46,XY mosaic cases. An accurate evaluation is necessary for a correct sex assignment and for surgical intervention to prevent neoplastic degeneration of the dysgenetic gonad. Orv. Hetil., 2012, 153, 303–307.


1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.


1997 ◽  
Vol 77 (02) ◽  
pp. 376-382 ◽  
Author(s):  
Bruce Lages ◽  
Harvey J Weiss

SummaryThe possible involvement of secreted platelet substances in agonist- induced [Ca2+]i increases was investigated by comparing these increases in aspirin-treated, fura-2-loaded normal platelets and platelets from patients with storage pool deficiencies (SPD). In the presence and absence of extracellular calcium, the [Ca2+]i response induced by 10 µM ADP, but not those induced by 0.1 unit/ml thrombin, 3.3 µM U46619, or 20 µM serotonin, was significantly greater in SPD platelets than in normal platelets, and was increased to the greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and normal platelets with 0.005-5 µM ADP produced a dose-dependent inhibition of the [Ca2+]i response induced by 10 µ M ADP, but did not alter the [Ca2+]i increases induced by thrombin or U46619. Within a limited range of ADP concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 µM ADP was significantly shifted to the right in SPD-HPS platelets, indicating that pre-incubation with greater amounts of ADP were required to achieve the same extent of inhibition as in normal platelets. These results are consistent with a hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal platelets may result from prior interactions of dense granule ADP, released via leakage or low levels of activation, with membrane ADP receptors, causing receptor desensitization. Addition of apyrase to platelet-rich plasma prior to fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD-HPS platelets, suggesting that some release of ADP derived from both dense granule and non-granular sources occurs during in vitro fura-2 loading and platelet washing procedures. However, this [Ca2+]i response was also greater in SPD-HPS platelets when blood was collected with minimal manipulation directly into anticoagulant containing apyrase, raising the possibility that release of dense granule ADP resulting in receptor desensitization may also occur in vivo. Thus, in addition to enhancing platelet activation, dense granule ADP could also act to limit the ADP-mediated reactivity of platelets exposed in vivo to low levels of stimulation.


2020 ◽  
Vol 13 (12) ◽  
pp. e237076
Author(s):  
George Vatidis ◽  
Eirini I Rigopoulou ◽  
Konstantinos Tepetes ◽  
George N Dalekos

Hepatic brucelloma (HB), a rare manifestation of brucellosis, refers to liver involvement in the form of abscess. A 35-year-old woman stockbreeder was admitted due to 1-month history of evening fever, sweating and weight loss, while she was on 3-week course of rifampicin/doxycycline for suspected brucellosis. On admission, she had hepatosplenomegaly and a systolic murmur, while cholestasis, increased inflammation markers and a strong-positive Wright-Coombs test were the main laboratory findings. As blood and bone marrow cultures were unrevealing, further investigation with CT imaging showed a central liver calcification surrounded by heterogeneous hypodense area being compatible with HB. Material from CT-guided drainage tested negative for Brucella spp. After failure to improve on a 10-week triple regiment, surgical excision was decided and Brucella spp were identified by PCR. Our case highlights challenges in establishing HB diagnosis, which should be considered on the right epidemiological context and when serological and radiological evidence favour its diagnosis.


2021 ◽  
Vol 9 (5) ◽  
pp. 1107
Author(s):  
Wonho Choi ◽  
Yoshihiro Yamaguchi ◽  
Ji-Young Park ◽  
Sang-Hyun Park ◽  
Hyeok-Won Lee ◽  
...  

Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The expression of MazF-at caused cell growth inhibition, while cells with MazF-at co-expressed with MazE-at grew normally. In vivo and in vitro assays revealed that MazF-at inhibited protein synthesis by decreasing the cellular mRNA stability. Moreover, the catalytic residue of MazF-at was determined to be the 24th glutamic acid using site-directed mutagenesis. From the results, we concluded that MazF-at is a type II toxin-antitoxin system and a ribosome-independent endoribonuclease. Here, we characterized a TA system in A. tumefaciens whose understanding might help to find its physiological function and to develop further applications.


Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 298
Author(s):  
Daniele Focosi ◽  
Angelo Genoni ◽  
Ersilia Lucenteforte ◽  
Silvia Tillati ◽  
Antonio Tamborini ◽  
...  

Antibody-dependent enhancement (ADE) of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) infection has been hypothesized. However, to date, there has been no in vitro or in vivo evidence supporting this. Cross-reactivity exists between SARS CoV-2 and other Coronaviridae for both cellular and humoral immunity. We show here that IgG against nucleocapsid protein of alphacoronavirus NL63 and 229E correlate with the World Health Organization’s (WHO) clinical severity score ≥ 5 (incidence rate ratios was 1.87 and 1.80, respectively, and 1.94 for the combination). These laboratory findings suggest possible ADE of SARS CoV-2 infection by previous alphacoronavirus immunity.


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