Gonadotropin Action in Isolated Ovarian Luteal Cells: The Intermediate Role of Adenosine 3′, 5′ Cyclic Monophosphate in Hormonal Stimulation of Progesterone Synthesis

Sala, G; Dufau, Maria L.; Catt, Kevin J.

doi:10.1007/978-1-4684-3474-3_54

Cited by 23 publications

(26 citation statements)

References 6 publications

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“…Protein phosphorylation in serine/threonine residues is a primary mode of regulation of hormone-stimulated steroidogenesis (Dufau et al 1977, Sala et al 1979, Clark et al 1994. Recently, we demonstrated that the ACTH signaling pathway also includes tyrosine dephosphorylation (Paz et al 1999).…”

Section: Discussionmentioning

confidence: 99%

“…In order to test this hypothesis, studies of PTP activity were extended to another steroidogenic system, as Leydig cells, using fresh interstitial testicular and MA-10 cells, an established and well-characterized tumor Leydig cell line (Ascoli 1981, Stocco & Chaudhary 1990, Stocco & Ascoli 1993, Weiss-Messer et al 1998. Testosterone production by Leydig cells in the testis is triggered by luteinizing hormone (LH) through cell surface receptors coupled to a signaling transduction mechanism based on PKAmediated phosphorylation (Dufau et al 1977, Clark et al 1994, a similar pathway to ACTH-activated corticosteroid production in adrenal zona fasciculata (ZF) (Podestá et al 1979, Sala et al 1979.…”

Section: Introductionmentioning

confidence: 99%

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LH/chorionic gonadotropin signaling pathway involves protein tyrosine phosphatase activity downstream of protein kinase A activation: evidence of an obligatory step in steroid production by Leydig cells

Maciel

Poderoso²,

Gorostizaga³

et al. 2001

Journal of Endocrinology

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Our recent reports indicate that protein tyrosine phosphorylation is an obligatory component of the mechanism of action of ACTH in its stimulatory action of corticosteroid production in adrenal zona fasciculata (ZF). The role of protein tyrosine phosphatase (PTP) activity in the regulation of steroidogenesis by LH/chorionic gonadotropin (CG) was tested using cell-permeable PTP inhibitors. Thus, PTP inhibition blocks LH-and 8-bromo-cAMP-stimulated testosterone production by Leydig cells without affecting 22(R)OH-cholesterolsupported steroidogenesis, similar results to those obtained in the adrenal ZF/ACTH system, leading us to propose that PTP action is an obligatory and common step in the cascade triggered by both hormones. Then, we continued the study testing whether LH modulates PTP activity in MA-10 cells, a Leydig cell line. In this regard, we observed by an in-gel PTP assay two PTPs of 110 and 50 kDa that are activated by hormone and 8-bromocAMP activation of the cells. Moreover, there is a transient increase by the second messenger in total PTP activity that correlates with the higher activity displayed by the 110 and 50 kDa proteins in the in-gel assay. In accordance with these results, analysis of tyrosine phosphorylated proteins showed the LH-induced dephosphorylation of proteins of 120, 68 and 50 kDa. The results of this study indicate that PTPs play an important role in the regulation of Leydig cell functions and that there exists a cross talk between serine/threonine phosphorylation and tyrosine dephosphorylation mediated by hormone-activated cAMP-dependent protein kinase and PTPs. These results are the first evidence of PTP having a role in LH/CGstimulated steroidogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LH/chorionic gonadotropin signaling pathway involves protein tyrosine phosphatase activity downstream of protein kinase A activation: evidence of an obligatory step in steroid production by Leydig cells

Maciel

Poderoso²,

Gorostizaga³

et al. 2001

Journal of Endocrinology

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“…1). Thus, adrenocorticotropic hormone (ACTH) stimulates glucocorticoid (cortisol/corticosterone) in adrenocortical fasiculata-reticularis cells [41,42]; ACTH or angiotensin II increases mineralocorticoid, aldosterone synthesis in adrenal glomerulosa cells [43,44]; human chorionic gonadotropin (hCG) or luteinizing hormone (LH) promotes progesterone synthesis in luteinized granulosa-luteal cells [45,46]; folliclestimulating hormone (FSH) stimulates progesterone and estrogen synthesis in granulosa cells [47,48]; and LH regulates androgen production both in theca-interstitial cells (androsterone) [49,50] and testicular Leydig cells (testosterone) [51,52].…”

Section: Hormonal Regulation Of Steroidogenesismentioning

confidence: 99%

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Zaidi¹

2013

TOLSJ

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Steroid hormones are lipophilic, low-molecular weight organic compounds all of which are derived from cholesterol. They are primarily synthesized by steroidogenic glands such as gonads (ovary and testis), the adrenal gland and, during pregnancy, by the placental trophoblasts. Limited steroid synthesis also takes place in the brain. Steroid hormones are crucial for the proper functioning of the body. They mediate a wide variety of vital physiological functions, ranging from maintaining normal reproductive function and secondary sexual characteristics, to regulating virtually every metabolic process in the body. Like many age-related endocrine disorders, aging also progressively impacts the tissue-specific synthesis and secretion of steroid hormones. The goal of this review is to summarize the effects of aging on steroid hormone synthesis and secretion by the adrenal gland and gonads of both human and experimental animal models, to describe the potential involvement of excessive oxidative stress in mediating age-related alterations in steroidogenesis, and to discuss the possible underlying mechanisms involved.

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“…While LH is the major physiological agonist in most animals, its action can also be mimicked by chorionic gonadotropin (CG). The signal transduction cascade involved in LH/CG action includes increases in intracellular cAMP levels and activation of protein kinase A (PKA), events that also occur in adrenocorticotropin (ACTH)-stimulated steroid production in adrenal cortical cells (Cooke et al 1976, Dufau et al 1977, Podestá et al 1979, Rae et al 1979, Sala et al 1979, Wang & Ascoli 1990, Swinnen et al 1991. It is well recognized that one of the requirements for full steroidogenic activity in response to LH/CG and ACTH is the PKA-mediated phosphorylation of regulatory proteins (Pon et al 1986, Chaudary & Stocco 1991, Stocco & Clark 1993.…”

Section: Introductionmentioning

confidence: 99%

Protein tyrosine phosphatases are involved in LH/chorionic gonadotropin and 8Br-cAMP regulation of steroidogenesis and StAR protein levels in MA-10 Leydig cells

Paz

Maciel²,

Maloberti³

et al. 2002

Journal of Endocrinology

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The LH signal transduction pathway features the activation of protein tyrosine phosphatases (PTPs) as one of the components of a cascade that includes other well characterized events such as cAMP-dependent protein kinase A (PKA) activation. Moreover, the action of PTPs is required to increase the rate-limiting step in steroid biosynthesis, namely the cAMP-regulated transfer of cholesterol to the inner mitochondrial membrane. Since both PKA activity and steroidogenic acute regulatory (StAR) protein induction are obligatory steps in this transfer of cholesterol, the present study was performed to investigate the role of PTPs in the regulation of PKA activity and StAR expression in response to LH/chorionic gonadotropin (CG) and 8Br-cAMP in MA-10 cells. While the exposure of MA-10 cells to the PTP inhibitor, phenylarsine oxide (PAO), did not modify PKA activity, it partially inhibited the effect of human CG and cAMP analog on StAR protein levels. Time-course studies demonstrated that PAO inhibited cAMP induction of StAR protein and mRNA. At 30 min, the effect on cAMPstimulated StAR protein levels was a 35% inhibition, progressing to up to 90% inhibition at 120 min of stimulation. The maximal inhibitory effect on cAMP-induced StAR mRNA level was obtained at 60 min (85%). In summary, these results demonstrate that inhibition of PTP activity affected both StAR protein and mRNA synthesis and suggest that the activity of hormone-regulated PTPs is a requirement in the LH signaling cascade that results in the up-regulation of StAR protein and, subsequently, increased steroid synthesis.

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Gonadotropin Action in Isolated Ovarian Luteal Cells: The Intermediate Role of Adenosine 3′, 5′ Cyclic Monophosphate in Hormonal Stimulation of Progesterone Synthesis

Cited by 23 publications

References 6 publications

LH/chorionic gonadotropin signaling pathway involves protein tyrosine phosphatase activity downstream of protein kinase A activation: evidence of an obligatory step in steroid production by Leydig cells

LH/chorionic gonadotropin signaling pathway involves protein tyrosine phosphatase activity downstream of protein kinase A activation: evidence of an obligatory step in steroid production by Leydig cells

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

Protein tyrosine phosphatases are involved in LH/chorionic gonadotropin and 8Br-cAMP regulation of steroidogenesis and StAR protein levels in MA-10 Leydig cells

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