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PubMed1976

In vitro-metabolism of 3H-progesterone in human testicular tissue: II Prepubertal and adolescent boys.

Normal sexual maturation in the human male depends upon a thorough regulation of the intratesticular androgen biosynthesis at various ages. We have systematically analysed the intratesticular steriod metabolic pathways in 11 boys, and 5-15 years, by means of incubation of minor testicular biopsy specimens with 3H-progesterone as substrate. Seven boys had abnormally situated testicles, and four had normally descended testicles. For comparison, 3 rats (10, 15 and 90 days old) were also investigated. Significant steroidogenic activity could be demonstrated in all prepubertal testicular tissue specimens. The steroid metabolic products recovered were identical with those found in a previously reported series of nine adult males (Kjessler & Berg, 1976), i.e., 20a-dihydroprogesterone, 17a-hydroxyprogesterone, 20a,17a-dihydroxyprogesterone, androstenedione and testosterone. No appreciable amounts of 5a-reduced substances were found. The steroid metabolic patterns observed in the present prepubertal and adolescent testicles differed from those found in adult males especially by their dissimilar proportions of newly synthesized 20a-dihydroprogesterone and 17a-hydroxyprogesterone. In prepubertal testicular tissue below the age of 11, 20a-dihydroprogesterone accounted for 45-82 per cent, and 17a-hydroxyprogesterone for only 3-6(-17) per cent of all metabolites formed. The steroid metabolic patterns displayed by abnormally situated testicles did not differ from those of normally descended testicles. The variation in steroid metabolic patterns observed between prepubertal and adult testicular tissue may be explained by the existing difference in physiologic gonadotrophic stimulation. It It may also be the result of an age-dependent maturation in various enzyme systems. The regulation of androgen biosynthesis with increasing age in the human male gonads does not seem to involve any significant reduction by 5a-reductase of continuously produced androgens, as in the immature rat. 2nstead, it appears to be brought about by a gradual shift in the metabolic pathways preferred by means of an increased activity of 17a-hydroxylase.

20-alpha-Dihydroprogesterone↗
PubMed1976

In vitro-metabolism of 3H-progesterone in human testicular tissue: I Adult males.

Androgen biosynthesis in the male gonads may be analysed in some detail by means of in vitro incubation of minor testicular biopsy specimens with various radiolabelled steroid precursors. We have investigated nine adult human male voluteers without apparent gonadal dysfunction with regard to their in vitro metabolism of 3H-progesterone. The following metabolic compounds were recovered: 20a-dihydroprogesterone, 17a-hydroxyprogesterone, 20a, 17a-dihydroxyprogesterone, androstenedione and testosterone. No significant amounts of 5a-reduced delta4-3-oxo-steroids or oestrogens were found. The major metabolites formed were 20a-dihydroprogesterone and 17a-hydroxyprogesterone, which accounted for 13-49 per cent and 17-47 per cent, respectively, of all newly synthesized steroid compounds. Radiolabelled delta4-3-oxo-C19-metabolites were recovered in minor amounts only, possibly due to metabolic interference with the endogenous pool of cold mass compounds. The individual steroid metabolic patterns were found to be poorly related to the individual levels of FSH, ICSH (LH) and testosterone in the peripheral circulation. Adequate knowledge of the steroid metabolic pathways generally utilized in ordinary testicular tissue in vitro is a prerequisite for the evaluation of steroid metabolism in males with various types of gonadal dysfunction.

20-alpha-Dihydroprogesterone↗
PubMed1976

In vitro-metabolism of 3H-progesterone in human testicular tissue: III Males with extremely high and low levels of gonadotrophic hormones in the peripheral circulation; including one "XX-male".

Individual steroid metabolic patterns in testicular tissue seem to vary characteristically with increasing maturity, as previously demonstrated by means of in vitro incubation studies with 3H-progesterone as substrate (Kjessler & Berg 1976; Berg et al. 1976). In the present study, individual steroid metabolic patterns were determined in two hypergonadotrophic males, one of whom representing the first instance of an "XX-male" studied in detail with regard to intratesticular steroidogenesis, and one hypogonadotrophic, hypophysectomized male. The radiolabelled steroid metabolic products recovered in the present series of testicular incubates were identical with those earlier observed in various series of prepubertal, adolescent and adult testicular specimens, i.e., 20alpha-dihydroprogesterone, 17alpha-hydroxyprogesterone, 17alpha,20alpha-dihydroxy-progesterone, androstenedione and testosterone. Thus, again, no appreciable amounts of 5alpha-reduced compounds were found in the present hyper- and hypogonadotrophic individuals. However, the proportions of newly synthesized and recovered delta4-3-oxo-C21-steroids in this series, especially 20alpha-dihydroprogesterone and 17alpha-hydroxyprogesterone, were found to differ considerably with various gonadotrophic stimulations. Hence, the relative proportions of 17alpha-hydroxyprogesterone increased, whereas the relative proportions of 20alpha-dihydroprogesterone decreased, with increasing gonadotrophic stimulation. The present results sustain and further extend our previous assumption that the relative proportions of newly synthesized and recovered delta4-3-oxo-C21-steroids in testicular incubates in vitro, especially 20alpha-dihydroprogesterone and 17alpha-hydroxyprogesterone, are primarily related to the individual degree of physiologic gonadotrophic stimulation at the moment of testicular biopsy, and less related to an unspecific maturation of various steroid metabolic enzyme systems.

20-alpha-Dihydroprogesterone↗
PubMed1976

In vitro-metabolism of 3H-progesterone in human testicular tissue: IV Before and after long-term gonadotrophin treatment; including one 47, XYY-male.

Certain defects in the intratesticular androgen biogenetic system may lead to a significant impairment of gonadal function in total in the human male. In the present investigation, four males with impaired reproductive performance were analysed before and after long term treatment with gonadotrophic hormones with regard to their in vitro metabolism of 3H-progesterone in testicular incubates; one of whom representing the first instance of an XYY-male studied in some detail with regard to intratesticular steroidogenesis. A steroid metabolisc pattern of an "immature" type, i.e., possibly indicating a relative understimulation of the gonads by gonadotrophic hormones, in vivo, was found in one of the four patients, i.e., the XYY-male, inspite of normal levels of gonadotrophic hormones in the peripheral circulation. Gametic output was found to increase significantly during the course of gonadotrophin substitution therapy, and the individual steroid metabolic pattern also changed drastically towards a more mature type subsequent to therapy. In a second patients, who originally presented with completely immotile sperm, a certain shift in the steroid metabolic pattern was observed after the gonadotrophin therapy in favour of increasing relative amounts of 17a-hydroxyprogesterone, concurrent with a decreasing proportion of dead sperm, and a certain, though minimal, improvement in sperm kinetics. The last two patients, with originally mature types of in vitro steroid metabolism in testicular incubates, displayed no changes in steroid metabolic patterns or spermiogram qualities subsequent to the gonadotrophin therapy. However, one of them might have been azoospermic because of anatomical reasons. The present demonstration that an individual steroid metabolic pattern in testicular incubates under certain conditions may be deliberately modified as expected, by long term gonadotrophin therapy, further supports our previous suggestion that the relative proportions of newly synthesized and recovered deltal4-3-oxo-C21-steroids in testicular incubates, especially 20a-dihydroprogesterone and 17a-hydroxyprogesterone, may well reflect the actual gonadotrophic stimulation in a particular individual at the time of testicular biopsy. Investigations of individual steroid metabolic patterns in testicular incubates may therefore contribute useful information for the adequate selection of patients with disturbed gonadal function, who may benefit from gonadotrophin substitution therapy.

20-alpha-Dihydroprogesterone↗