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G Läckgren

Publications and source records attributed to G Läckgren.

51 records · Page 3Linked to original sources

Influence of hCG treatment on the metabolism of progesterone and pregnenolone in vitro by the human undescended prepubertal testis.

Testicular biopsies were taken from 56 prepubertal and pubertal boys, aged 3-17 years, with undescended testes. The biopsies were incubated in vitro with 3H-progesterone or 3H-pregnenolone. Fifteen of the boys had been treated with human chorionic gonadotrophin (hCG) prior to operation. Nine boys were operated on within 1 week of the last injection of hCG while the others were operated on between 12 days and 2 years after hCG treatment. In non-treated prepubertal boys very small amounts of substrate were converted by means of the enzymes 3 beta-hydroxysteroid-dehydrogenase and 17 alpha-hydroxylase and virtually no testosterone was produced. Immediately after treatment with hCG there was a large increase in the conversion of substrate by 17 alpha-hydroxylase and 3 beta-hydroxysteroid-dehydrogenase. Considerable amounts of testosterone were formed, especially from pregnenolone, while smaller amounts were formed from progesterone. This suggests that testosterone production occurred primarily via the delta 5 pathway, at least beyond the 17 alpha-hydroxylase-step. Within 2 weeks of the last hCG injection, steroidogenic activity had decreased towards levels similar to those found in prepubertal testis from untreated boys. These observations indicate that hCG treatment of boys with undescended testes does not result in irreversible or even long-lasting stimulation of their steroidogenic function.

Adolescent↗

An XXX male resulting from paternal X-Y interchange and maternal X-X nondisjunction.

A 2-year-old boy was found to have a 47,XXX karyotype. Restriction-fragment-length-polymorphism analysis showed that, of his three X chromosomes, one is of paternal and two are of maternal origin. The results of Y-DNA hybridization were reminiscent of those in XX males in two respects. First, hybridization to Southern transfers revealed the presence in this XXX male of sequences derived from the Y-chromosomal short arm. Second, in situ hybridization showed that this Y DNA was located on the tip of the X-chromosomal short arm. We conclude that this XXX male resulted from the coincidence of X-X nondisjunction during maternal meiosis and aberrant X-Y interchange either during or prior to paternal meiosis.

Child, Preschool↗

The morphology of the human undescended testis with special reference to the Sertoli cell and puberty.

The morphology of the undescended testis was studied in 50 boys aged 1-15 years. A low mean number of spermatogonia was found, but there were marked differences between the boys, some having high numbers whereas others were devoid of spermatogonia. Most Sertoli cells did not undergo normal maturation during puberty, but instead seemed to proliferate at a slow rate. It is concluded that treatment of undescended testes should be performed during the prepubertal period. It is also suggested that some undescended testes have a primary defect whereas others are damaged during the onset of puberty.

Adolescent↗

The influence of human chorionic gonadotrophin (hCG) on the morphology of the prepubertal human undescended testis.

The effect of hCG-treatment on the morphology of the undescended testis was studied in testicular biopsies from 36 prepubertal boys operated on at intervals of 1 day to 2 years after discontinuation of hormonal treatment. Immediately after treatment, mature Leydig cells were observed, and the Sertoli cells were increased in size; serum testosterone had increased to adult levels. All these changes were reversible as judged from the material taken one month or more after the last hCG injection. Based on the observations and the results of a previous study it is suggested that hCG treatment does not induce any premature onset of Sertoli cell or germ cell maturation either in the undescended or in the contralateral testis.

Biopsy↗

In vitro conversion of 3H-pregnenolone by human testicular tissue from fetal age to senescence.

The in vitro conversion of pregnenolone was studied in testicular tissue specimens from 6 fetuses, 3 prepubertal boys with undescended testes, 5 normal adult men, and 12 elderly males with prostatic carcinoma. Adult testicular tissue converted pregnenolone to testosterone mainly along the delta 5 metabolic pathway. Steroid intermediates that were converted from pregnenolone to delta 4 metabolites prior to the rate limiting C17-20 lyase step were "trapped" as 17 alpha-hydroxyprogesterone. The conversion patterns in testicular tissue from fetuses were similar to those in testicular tissue from adults and elderly men. In prepubertal testicular tissue, however, a significantly lower conversion was observed, mediated by the enzymes 3 beta-hydroxysteroid dehydrogenase/isomerase and 17 alpha-hydroxylase. The conversion mediated by 17 alpha-hydroxylase was significantly lower in testicular tissue from the elderly males than from younger adults, suggesting a relative steroidogenic insufficiency in the elderly males. Testicular tissue from an anencephalic fetus produced testosterone and steroid intermediates in vitro, although to a lesser extent than in testicular tissue from other fetuses. The enzymes 3 beta-hydroxysteroid dehydrogenase/isomerase and 17 alpha-hydroxylase appeared to be under gonadotropic control.

3-Hydroxysteroid Dehydrogenases↗

Germ cell adenylyl cyclase activity in the human undescended testis and the effect of HCG-treatment.

In the present study we have examined the soluble Mn2+ dependent, germ cell specific adenylyl cyclase (AC) activity and germ cell morphology in testicular biopsies from twenty-three boys, aged 2-17 years, with undescended testes and three adult men with normally descended testes. Eight of the boys were treated with hCG immediately before surgery. Germ cell AC-activity (3.2-3.4 pmoles cAMP/mg protein/min) was found in the adult testes with normal germ cell morphology. Furthermore, low but significant AC-activity (0.2-0.8 pmoles cAMP/mg protein/min) was noted in biopsies containing only primary spermatocytes. There was no Mn2+ dependent AC-activity in Sertoli cell only testes or in testes where only spermatogonia were observed. Treatment with hCG did not influence germ cell maturation or soluble Mn2+ dependent AC-activity.

Adenylyl Cyclases↗

Neuron-specific enolase as a differential marker in a case of retroperitoneal tumour.

In some cases of retroperitoneal tumour, preoperative investigations fail to conclusively differentiate between neuroblastoma and Wilms' tumour. Diagnostic difficulties can be encountered also intraoperatively, and even the histopathological presentation can be equivocal. According to earlier results, neuron-specific enolase (NSE) in tumour extract can be used as a marker for neuronal tissue and thus offers a new diagnostic criterion differing neuroblastoma from e.g. Wilms' tumour. This paper presents a case of Wilms' tumour where a low content of NSE in the tumour extract correctly indicated a non-neuronal tumour, whereas preoperative presentation and primary histopathology suggested a neuroblastoma.

Child↗

Receptors for luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the human undescended testis and the effect of hCG-treatment.

Human testis tissue contains specific receptors for luteinizing hormone (LH) and follicle stimulating hormone (FSH) with Ka's of 1.5 and 1.6 X 10(9) M-1, respectively. Specific binding of [125I]hLH and [125I]hFSH was studied in testicular biopsies from 33 boys (4-16 years of age) with undescended testes and in 2 adult men with normally descended testes. Ten of the boys were treated with human chorionic gonadotrophin (hCG) and operated 1-4 days after the last injection. Samples from each testis were taken for histological evaluation. Specific binding of LH in biopsies from pre-pubertal boys (stage I) was low and differentiated Leydig cells could not be identified histologically. In later pubertal stages the LH binding increased and differentiated Leydig cells could now be recognized. hCG-treatment caused a highly significant increase (P less than 0.001) in the binding of LH without affecting FSH binding. The highest binding of FSH occurred during the onset of puberty. Treatment with hCG did not cause premature differentiation of Sertoli cells or germ cells, but appeared to stimulate Leydig cells.

Adolescent↗

The effect of hCG-treatment on in vitro metabolism of progesterone by the human undescended pre-pubertal testis.

Testicular biopsies from 8 pre-pubertal boys aged 3 1/2-11 years, with undescended testes, were incubated in vitro with [3H]progesterone (P). All boys had been treated with human chorionic gonadotrophin (hCG) during the 5 weeks prior to surgery. Four boys were operated within 4 days of the last injection and the remaining 4 at 12 days, 14 days, 6 months and 12 months, respectively, after hormone treatment. Significant steroid metabolic activity was demonstrated in all cases. Biopsies taken a short time after hCG-treatment (1-4 days), when blood testosterone levels were high, exhibited a high capacity for metabolizing progesterone in vitro with a low ratio of formed 20 alpha-dihydro-progesterone (20 alpha-DH-P) to 17 alpha-hydroxyprogesterone (17 alpha-OH-P), when compared to biopsies removed from subjects 12-14 days after cessation of treatment. In the latter cases and in biopsies taken at longer intervals after hormone treatment, the metabolic activity and the 20 alpha-DH-P/17 alpha-OH-P ratio had returned to levels characteristic of untreated pre-pubertal cryptorchid testes. These findings indicate that the use of hCG to provoke descent of the malpositioned testes does not result in long-lasting stimulation of steroidogenic function.

Biopsy↗

In vitro metabolism of progesterone by the human undescended testis.

Testicular biopsy specimens from 28 boys with undescended testis, and from 6 men operated post-pubertally for undescended testis, were incubated in vitro with [3H]progesterone (P). Significant steroid metabolic activity was demonstrated in all biopsies. Before puberty the total conversion rate was low and only a small amount of 17 alpha-hydroxy-progesterone (17 alpha-OH-P) was formed. The amount of newly formed 20 alpha-dihydro-progesterone (20 alpha-DH-P) was relatively constant regardless of increasing maturity. After puberty the total conversion rate was higher. More 17 alpha-OH-P was synthesized, and the ratio between formed 20 alpha-DH-P and 17 alpha-OH-P decreased significantly. The position of the undescended testis did not appear to influence progesterone metabolism. In no case could we demonstrate deficient steroidogenesis. In one 17-year old boy the 20 alpha-DH-P/17 alpha-OH-P ratio was lower in the undescended testis (0.9) than in the scrotal testis (4.0) suggesting increased steroidogenesis per mg tissue in the malpositioned testis. The indication from the present study, that even grossly displaced testes have a relatively undisturbed steroidogenic capability, suggests that the reason for impaired descent may not simply reflect disturbed androgen synthesis, but must involve other mechanisms.

Adolescent↗

Neuron specific enolase: a marker for differential diagnosis of neuroblastoma and Wilms' tumor.

Thirteen human neuroblastoma and six Wilms' tumor biopsies have been analyzed for neuron specific enolase (NSE). THe relative activity of NSE in the neuroblastomas (including ganglioneuroblastoma and ganglioneuroma) ranged from 28% to 62.5% of total enolase activity. The corresponding figures for the Wilms' tumors were 1% to 4.5%. It appears that NSE can serve as a biochemical marker for neuroblastoma and be useful in the differential diagnosis of neuroblastoma and Wilms' tumor.

Child↗

Neuron-specific enolase in relation to differentiation in human neuroblastoma.

The presence of the two forms of enolase, neuron-specific enolase (NSE) and non-neuronal enolase (NNE), have been examined in biopsy material of human neuroblastoma, ganglioneuroblastoma, ganglioneuroma and cultured neuroblastoma cells, after separation with ion exchange chromatography. The enolase activities were inhibited in the presence of NaCl but remained active in KCl, which were used in the chromatographic step. The relative NSE levels in the neuroblastoma tissues were found to be lower than in the histopathologically more differentiated forms of the tumour, i.e. ganglioneuroblastoma and ganglioneuroma. The human neuroblastoma in vitro cell lines SK-N-SH, SH-SY5Y, SK-N-MC and IMR-32 contained considerably lower relative levels of NSE compared to the levels in the neuroblastoma biopsies. After treatment of the cultured cells with nerve growth factor or dibutyryl-cAMP some cells showed morphological differentiation and concomitantly an increase in the NSE levels. The results indicate that NSE might be useful as a marker for differentiation in human neuroblastoma.

Biopsy↗

On the in vitro metabolism of androstenedione and progesterone in human testicular tissue from fetal age to senescence.

The conversion of [3H]-androstenedione to testosterone regulated by the enzyme 17 beta-ketosteroid reductase and the conversion of [3H]-progesterone to 17 alpha-hydroxyprogesterone and onwards along the delta 4 metabolic pathway was studied in vitro in human testicular tissue from 32 males (2 fetuses, 25 adult, infertile men and 5 elderly men with prostatic carcinoma). Additionally, two prepubertal boys were studied with respect to the conversion of [3H]-androstenedione to testosterone in vitro, whereas another seven boys were studied with reference to the conversion of [3H]-progesterone in vitro. It appeared, that in all cases, the conversion of androstenedione to testosterone was larger than the conversion of progesterone to 17 alpha-hydroxyprogesterone by way of the 17 alpha-hydroxylase and onwards along the delta 4 metabolic pathway. It is thus concluded that the 17 beta ketosteroid reductase is not a rate-limiting enzyme along the delta 4 metabolic pathway. No case of deficient 17 beta-ketosteroid reductase was found among the 25 infertile patients studied.

Adolescent↗

Significance of collateral arterial supply to Wilms' tumours.

The presence of collateral arterial supply was examined by angiography in 19 children with Wilms' tumour. Collateral arterial supply was related to tumour size. Ten of 14 tumours displaying collateral circulation were entirely intrarenal at operation, confirmed by histopathology. Angiography in Wilms' tumour is indicated when the results of urography, ultrasonography or computed tomography are equivocal or extrarenal tumour growth is suggested.

Adolescent↗