A change in the steroid metabolic pathway in human testes showing deteriorated spermatogenesis
| Autor: | Shiari Nozawa, Teruaki Iwamoto, Kiyoshi Asahina, Miki Yoshiike, Yoko Sato, Takeshige Otoi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Varicocele Obstructive azoospermia Biology Gene Expression Regulation Enzymologic 03 medical and health sciences 0302 clinical medicine Endocrinology Testicular Neoplasms Internal medicine Cryptorchidism Testis medicine Humans Testosterone Spermatogenesis Infertility Male Progesterone Azoospermia 030219 obstetrics & reproductive medicine Steroid 17-alpha-Hydroxylase medicine.disease 030104 developmental biology CYP17A1 Pregnenolone Androgens Animal Science and Zoology Developmental Biology Hormone medicine.drug |
| Zdroj: | Reproductive biology. 20(2) |
| ISSN: | 2300-732X |
| Popis: | During androgen biosynthesis, the human testes normally produce only small quantities of Δ4-C21 steroids as these are products of the Δ4-pathway and healthy human testes preferentially use the Δ5-pathway. However, the Δ4-C21 steroid progesterone accumulates in the thickened lamina propria of the seminiferous tubules in testes with deteriorated spermatogenesis. The objectives of this study were to analyse the pregnenolone metabolites in testes with deteriorated spermatogenesis and to establish whether the androgen biosynthesis pathway changes in this condition. Biopsied or orchiectomised testicular samples were obtained from patients with varicocele, non-obstructive azoospermia, obstructive azoospermia, testicular cancer, and cryptorchidism. The samples were segregated into spermatogenesis related Johnsen's score groups: Low-JS ( 7.8). Higher levels of progesterone and 17α-hydroxyprogesterone were metabolised under in vitro conversion in the Low-JS testes than the High-JS testes when cell-free homogenates from each group were separately incubated with 14C-labelled pregnenolone. Nevertheless, the serum hormone levels did not differ between groups. Two novel pregnenolone metabolites 5β-pregnan-3β-ol-20-one and 5α-pregnan-3α, 21diol-20-one were identified from in vitro conversion in Low-JS testes and by recrystallisation. Immunohistochemistry revealed the higher βHSD expression in the Low-JS than the High-JS testes. However, the CYP17A1 expression levels did not differ between groups. Infertile testes increase the relative βHSD levels in their Leydig cells and synthesised testosterone from pregnenolone via the Δ4- rather than the Δ5-pathway. A new insight into a change of metabolites in Low-JS testes will be relevant to understand the mechanism of the deteriorated spermatogenesis under the normal range of testosterone level. |
| Databáze: | OpenAIRE |
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