Changes in ovarian 5α-steroid reductase and 20α-hydroxysteroid dehydrogenase activity produced by induction of first ovulation with gonadotropin

Eckstein, B.; Lerner, Nicole

doi:10.1016/0005-2760(77)90240-5

Cited by 22 publications

(2 citation statements)

References 13 publications

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“…Moreover, subsequent to the first ovulation, the 5a-reductase activity is substantially attenuated, while the activity of 20a-HSD is markedly increased. 28 Figure 4 demonstrates that KCZ does not affect the 20a-HSD activity. Residual conversion of 20a-OHP to pregnanediol, via a low reductase and 3a-HSD activities, corroborate that KCZ does not affect those noncytochrome enzymes.…”

Section: Discussionmentioning

confidence: 97%

Selective Inhibition of Steroidogenic Enzymes by Ketoconazole in Rat Ovary Cells

Gal

Orly

2014

Clin Med�Insights�Reprod�Health

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OBJECTIVEKetoconazole (KCZ) is an anti-fungal agent extensively used for clinical applications related to its inhibitory effects on adrenal and testicular steroidogenesis. Much less information is available on the effects of KCZ on synthesis of steroid hormones in the ovary. The present study aimed to characterize the in situ effects of KCZ on steroidogenic enzymes in primary rat ovary cells.METHODSFollowing the induction of folliculogenesis in gonadotropin treated rats, freshly prepared ovarian cells were incubated in suspension for up to four hours while radiolabeled steroid substrates were added and time dependent generation of their metabolic products was analyzed by thin layer chromatography (TLC).RESULTSKCZ inhibits the P450 steroidogenic enzymes in a selective and dose dependent manner, including cholesterol side-chain cleavage cytochrome P450 (CYP11A1/P450scc), the 17α-hydroxylase activity of CYP17A1/P450c17, and CYP19A1/P450arom, with IC50 values of 0.3, 1.8, and 0.3 μg/mL (0.56, 3.36, and 0.56 μM), respectively. Unaffected by KCZ, at 10 μg/mL, were the 17,20 lyase activity of CYP17A1, as well as five non-cytochrome steroidogenic enzymes including 3β-hydroxysteroid dehydrogenase-Δ5–4 isomerase type 1 (3βHSD1), 5α-reductase, 20α-hydroxysteroid dehydrogenase (20α-HSD), 3α-hydroxysteroid dehydrogenase (3α-HSD), and 17β-hydroxysteroid dehydrogenase type 1 (17HSD1).CONCLUSIONThese findings map the effects of KCZ on the ovarian pathways of progestin, androgen, and estrogen synthesis. Hence, the drug may have a potential use as an acute and reversible modulator of ovarian steroidogenesis in pathological circumstances.

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Section: Discussionmentioning

confidence: 97%

Selective Inhibition of Steroidogenic Enzymes by Ketoconazole in Rat Ovary Cells

Gal

Orly

2014

Clin Med�Insights�Reprod�Health

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“…This implies necessary changes in the ovarian machinery before it can be induced to ovulate. Indeed, Eckstein & Lerner (1978) have shown that the earliest event connected with the first ovulation in rodents is a sharp decrease in ovarian 5cr-reductase activity. This change in steroid metabolism, and its consequent reduction in 5cr-reduced androgens, would shift the balance, as described earlier (Text- fig.…”

Section: Maturation Of the Feedback Mechanismmentioning

confidence: 99%

The ovary learns to ovulate

et al. 1978

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Sensory stimuli from the external environment (e.g. visual and olfactory stimuli, stress) or internal stimuli cause brain nerve fibres to release neurotransmitters (catecholamines, indolamines and cholinergic agents). These neurotransmitters regulate the secretion of gonadotrophin-releasing hormone (GnRH) from neurosecretory cells of the hypothalamus (Kamberi, 1975). It would seem that under the proper steroid environment, catecholamines (dopamine, norepinephrine or epinephrine) and the cholinergic agent acetylcholine exert a stimulatory influence, whereas indolamines (serotonin or its metabolic product, melatonin) have an opposite effect. In turn, GnRH reaches the anterior pituitary via the hypophyseal portal system, and, through the mediation of cAMP [though may be not as an obligatory intermediate (Naor et al., 1975)], controls gonadotrophin secretion (Labrie et al., 1974).

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Role of ovarian thecal and granulosa layers in gonadotropin-induced synthesis of a salmonid maturation-inducing substance (17α,20β-dihydroxy-4-pregnen-3-one)

Young

Adachi

Nagahama

1986

Developmental Biology

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Changes in ovarian 5α-steroid reductase and 20α-hydroxysteroid dehydrogenase activity produced by induction of first ovulation with gonadotropin

Cited by 22 publications

References 13 publications

Selective Inhibition of Steroidogenic Enzymes by Ketoconazole in Rat Ovary Cells

Selective Inhibition of Steroidogenic Enzymes by Ketoconazole in Rat Ovary Cells

The ovary learns to ovulate

Role of ovarian thecal and granulosa layers in gonadotropin-induced synthesis of a salmonid maturation-inducing substance (17α,20β-dihydroxy-4-pregnen-3-one)

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