Luteinizing hormone induction of the cholesterol side-chain cleavage enzyme in cultured immature rat Leydig cells: No role of insulin-like growth factor-I?

Haren, Lizzy van; Flinterman, J F; Orly, Joseph; Rommerts, F. F. G.

doi:10.1016/0303-7207(92)90233-v

Cited by 15 publications

(10 citation statements)

References 56 publications

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“…IGF-l is produced locally in many tissues and in combination with the six different IGF binding proteins, the IFG/IGF-BP system has been proposed as a super-system for fine tuning of local hormone action. In contrast with this model, IGF-l did not affect LH-induced cholesterol side chain cleavage enzyme activity in cultured Leydig cells (van Haren et al 1992). Many in vitro studies have shown that this IGF-l system can also influence Leydig cells.…”

Section: Regulation Of Androgen Synthesis By Locally Produced Factorscontrasting

confidence: 77%

Testosterone: An overview of biosynthesis, transport, metabolism and nongenomic actions

Rommerts¹

1998

Testosterone

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Section: Regulation Of Androgen Synthesis By Locally Produced Factorscontrasting

confidence: 77%

Testosterone: An overview of biosynthesis, transport, metabolism and nongenomic actions

Rommerts¹

1998

Testosterone

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“…No significant effect of IGF-I was observed on either P450scc or 3␤-HSD protein levels in mLTC-1 cells. Likewise, IGF-I had no effect on P450scc mRNA expression, although it increases hCG-stimulated P450scc levels in primary cultures of rat Leydig cells (64,65). An elevation of P450scc and 17␣-hydroxylase mRNA levels in porcine Leydig cells has also been reported (10).…”

Section: Discussionmentioning

confidence: 85%

Molecular Mechanisms of Insulin-like Growth Factor-I Mediated Regulation of the Steroidogenic Acute Regulatory Protein in Mouse Leydig Cells

Manna

Chandrala

King

et al. 2006

Molecular Endocrinology

116

108

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Growth factors are known to play diverse roles in steroidogenesis, a process regulated by the mitochondrial steroidogenic acute regulatory (StAR) protein. The mechanism of action of one such growth factor, IGF-I, was investigated in mouse Leydig tumor (mLTC-1) cells to determine its potential role in the regulation of StAR expression. mLTC-1 cells treated with IGF-I demonstrated temporal and concentration-dependent increases in StAR expression and steroid synthesis. However, IGF-I had no effect on cytochrome P450 side-chain cleavage or 3beta-hydroxysteroid dehydrogenase protein levels. IGF-I was capable of augmenting N,O'-dibutyrl-cAMP-stimulated steroidogenic responsiveness in these cells. The steroidogenic potential of IGF-I was also confirmed in primary cultures of isolated mouse Leydig cells. IGF-I increased phosphorylation of ERK1/2, an event inhibited by the MAPK/ERK inhibitors, PD98059 and U0126. Interestingly, inhibition of ERK activity enhanced IGF-I-mediated StAR protein expression, but phosphorylation of StAR was undetectable, an observation in contrast to that seen with N,O'-dibutyrl-cAMP signaling. Further studies demonstrated that these events were tightly correlated with the expression of dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene 1 and scavenger receptor class B type 1. Whereas both protein kinase A and protein kinase C signaling were involved in the IGF-I-mediated steroidogenic response, the majority of the effects of IGF-I were found to be mediated by the protein kinase C pathway. Transcriptional activation of the StAR gene by IGF-I was influenced by several transcription factors, its up-regulation being dependent on phosphorylation of the cAMP response element-binding protein (CREB) and the activator protein 1 family member, c-Jun. Conversely, StAR gene transcription was markedly inhibited by expression of nonphosphorylatable CREB (Ser(133)Ala), dominant negative A-CREB, and dominant negative c-Jun (TAM-67) mutants. Collectively, the present studies identify molecular events in IGF-I signaling that may influence testicular growth, development, and the Leydig cell steroidogenic machinery through autocrine/paracrine regulation.

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“…One possible explanation is that the absence of IGF-I stimulation results in a developmental delay, with the LC lineage arrested at the PLC stage of differentiation, which is relatively unresponsive to IGF-I or LH stimulation. In vitro studies have shown that ILCs [42,43] are more responsive than progenitor LCs [44] to IGF-I1-stimulated steroidogenesis [40,45,46]. The absence of IGF-I action is also associated with a decrease in testicular LHR [47], which may explain the attenuated action of exogenously-administered LH on LCs.…”

Section: Discussionmentioning

confidence: 97%

Development of Leydig Cells in the Insulin-Like Growth Factor-I (IGF-I) Knockout Mouse: Effects of IGF-I Replacement and Gonadotropic Stimulation1

Wang

Hardy

2004

Biology of Reproduction

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Targeted gene deletion of insulin-like growth factor-I (IGF-I) results in diminished numbers of Leydig cells (LCs) and lower circulating testosterone (T) levels in adult males. The impact of endogenous IGF-I withdrawal on proliferation (labeling index, LI) and differentiation of LCs was investigated, testing for restorative effects of IGF-I replacement and/or LH stimulation. With IGF-I replacement in mutant mice, LIs increased more than 200% (P < 0.05). LC numbers were also increased by 200%, whereas the numbers of intermediate cell progenitors (PLCs) were unchanged compared to mutant vehicle controls. LIs of PLCs in wild-type males increased by 200% after LH stimulation, and LC numbers increased by 50% compared to vehicle-treated controls (P < 0.05). In contrast, there was no effect of LH on LI in mutant mice, but LC numbers still increased by 30% (P < 0.05). Additive effects on LI and cell numbers were observed in response to IGF-I plus LH in mutants, implying that the two hormones use separate signaling pathways. Serum T and LH levels in wild-type and mutant males were equivalent. Exogenous LH increased T production 8-fold in wild-type males (P < 0.01). In mutant mice, neither LH stimulation nor IGF-I alone affected serum T levels, but IGF-I plus LH stimulation increased serum T 2-fold (P < 0.05). These data support the conclusions that 1) IGF-I is a critical autocrine and/or paracrine factor in the control of adult LC numbers and function; and 2) LH is not a direct mitogenic factor for LCs, and acts in part through IGF-I to stimulate proliferative activity.

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Luteinizing hormone induction of the cholesterol side-chain cleavage enzyme in cultured immature rat Leydig cells: No role of insulin-like growth factor-I?

Cited by 15 publications

References 56 publications

Testosterone: An overview of biosynthesis, transport, metabolism and nongenomic actions

Testosterone: An overview of biosynthesis, transport, metabolism and nongenomic actions

Molecular Mechanisms of Insulin-like Growth Factor-I Mediated Regulation of the Steroidogenic Acute Regulatory Protein in Mouse Leydig Cells

Development of Leydig Cells in the Insulin-Like Growth Factor-I (IGF-I) Knockout Mouse: Effects of IGF-I Replacement and Gonadotropic Stimulation1

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