Specificity of the direct effect of an LHRH agonist on testicular 17-hydroxylase but not on 5α-reductase activity in hypophysectomized adult rats

Yves Tremblay, Alain Bélanger, Bianca Marchetti

Research output: Contribution to journalArticle

Abstract

The direct effect of treatment with a potent LHRH agonist on testicular steroidogenesis was studied by incubation of radioactive steroids with a testicular homogenate or with a suspension of interstitial cells obtained following 7 days of treatment of adult hypophysectomized male rats. The animals received [D-ser(tBu)6,des-Gly-NH2 10]LHRH ethylamide (25 μg) administered 3 times a day, hCG (5 or 25 IU) once daily or a combination of both drugs. The metabolism of tritiated progesterone into Δ4-metabolites by a suspension of interstitial cells was markedly reduced by treatment with the LHRH agonist (LHRH-A) alone or following combined treatment with hCG and LHRH-A. No formation of 5α-reduced steroids was detected in the medium following incubation with testicular homogenate or interstitial cells. Similar findings were obtained by measurement of testicular steroid content. The present data demonstrate that the direct effect of the LHRH agonist is limited to the Leydig cells on 17-hydroxylase activity. This inhibitory effect is reflected by an accumulation of testicular pregnenolone and progesterone content and a marked inhibition of progesterone metabolism into Δ4-androgens. However, no stimulation of 5α-reductase, an enzyme localized in seminiferous tubules, could be detected. Such data show clear differences between the direct and the pituitary-mediated effects of treatment with LHRH agonists on testicular steroidogenesis. While the LHRH agonist administered at high doses in the rat can directly inhibit 17-hydroxylase activity, the stimulatory effect on 5α-reductase activity is regulated by another mechanism.

Original languageEnglish
Pages (from-to)33-40
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume40
Issue number1
DOIs
Publication statusPublished - 1985

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Mixed Function Oxygenases
Gonadotropin-Releasing Hormone
Rats
Oxidoreductases
Progesterone
Steroids
Metabolism
Suspensions
Enzyme inhibition
Pregnenolone
Seminiferous Tubules
Leydig Cells
Drug Combinations
Metabolites
Androgens
Animals
Enzymes

Keywords

  • direct effect
  • hypophysectomized
  • LHRH-A
  • steroidogenesis

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Specificity of the direct effect of an LHRH agonist on testicular 17-hydroxylase but not on 5α-reductase activity in hypophysectomized adult rats",
abstract = "The direct effect of treatment with a potent LHRH agonist on testicular steroidogenesis was studied by incubation of radioactive steroids with a testicular homogenate or with a suspension of interstitial cells obtained following 7 days of treatment of adult hypophysectomized male rats. The animals received [D-ser(tBu)6,des-Gly-NH2 10]LHRH ethylamide (25 μg) administered 3 times a day, hCG (5 or 25 IU) once daily or a combination of both drugs. The metabolism of tritiated progesterone into Δ4-metabolites by a suspension of interstitial cells was markedly reduced by treatment with the LHRH agonist (LHRH-A) alone or following combined treatment with hCG and LHRH-A. No formation of 5α-reduced steroids was detected in the medium following incubation with testicular homogenate or interstitial cells. Similar findings were obtained by measurement of testicular steroid content. The present data demonstrate that the direct effect of the LHRH agonist is limited to the Leydig cells on 17-hydroxylase activity. This inhibitory effect is reflected by an accumulation of testicular pregnenolone and progesterone content and a marked inhibition of progesterone metabolism into Δ4-androgens. However, no stimulation of 5α-reductase, an enzyme localized in seminiferous tubules, could be detected. Such data show clear differences between the direct and the pituitary-mediated effects of treatment with LHRH agonists on testicular steroidogenesis. While the LHRH agonist administered at high doses in the rat can directly inhibit 17-hydroxylase activity, the stimulatory effect on 5α-reductase activity is regulated by another mechanism.",
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author = "Yves Tremblay and Alain B{\'e}langer and Bianca Marchetti",
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T1 - Specificity of the direct effect of an LHRH agonist on testicular 17-hydroxylase but not on 5α-reductase activity in hypophysectomized adult rats

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AU - Bélanger, Alain

AU - Marchetti, Bianca

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N2 - The direct effect of treatment with a potent LHRH agonist on testicular steroidogenesis was studied by incubation of radioactive steroids with a testicular homogenate or with a suspension of interstitial cells obtained following 7 days of treatment of adult hypophysectomized male rats. The animals received [D-ser(tBu)6,des-Gly-NH2 10]LHRH ethylamide (25 μg) administered 3 times a day, hCG (5 or 25 IU) once daily or a combination of both drugs. The metabolism of tritiated progesterone into Δ4-metabolites by a suspension of interstitial cells was markedly reduced by treatment with the LHRH agonist (LHRH-A) alone or following combined treatment with hCG and LHRH-A. No formation of 5α-reduced steroids was detected in the medium following incubation with testicular homogenate or interstitial cells. Similar findings were obtained by measurement of testicular steroid content. The present data demonstrate that the direct effect of the LHRH agonist is limited to the Leydig cells on 17-hydroxylase activity. This inhibitory effect is reflected by an accumulation of testicular pregnenolone and progesterone content and a marked inhibition of progesterone metabolism into Δ4-androgens. However, no stimulation of 5α-reductase, an enzyme localized in seminiferous tubules, could be detected. Such data show clear differences between the direct and the pituitary-mediated effects of treatment with LHRH agonists on testicular steroidogenesis. While the LHRH agonist administered at high doses in the rat can directly inhibit 17-hydroxylase activity, the stimulatory effect on 5α-reductase activity is regulated by another mechanism.

AB - The direct effect of treatment with a potent LHRH agonist on testicular steroidogenesis was studied by incubation of radioactive steroids with a testicular homogenate or with a suspension of interstitial cells obtained following 7 days of treatment of adult hypophysectomized male rats. The animals received [D-ser(tBu)6,des-Gly-NH2 10]LHRH ethylamide (25 μg) administered 3 times a day, hCG (5 or 25 IU) once daily or a combination of both drugs. The metabolism of tritiated progesterone into Δ4-metabolites by a suspension of interstitial cells was markedly reduced by treatment with the LHRH agonist (LHRH-A) alone or following combined treatment with hCG and LHRH-A. No formation of 5α-reduced steroids was detected in the medium following incubation with testicular homogenate or interstitial cells. Similar findings were obtained by measurement of testicular steroid content. The present data demonstrate that the direct effect of the LHRH agonist is limited to the Leydig cells on 17-hydroxylase activity. This inhibitory effect is reflected by an accumulation of testicular pregnenolone and progesterone content and a marked inhibition of progesterone metabolism into Δ4-androgens. However, no stimulation of 5α-reductase, an enzyme localized in seminiferous tubules, could be detected. Such data show clear differences between the direct and the pituitary-mediated effects of treatment with LHRH agonists on testicular steroidogenesis. While the LHRH agonist administered at high doses in the rat can directly inhibit 17-hydroxylase activity, the stimulatory effect on 5α-reductase activity is regulated by another mechanism.

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