Insulin-Like Growth Factor-I Regulates Aromatase Activity in Human Granulosa and Granulosa Luteal Cells*

Erickson, Gregory F.; Garzo, V. Gabriel; Magoffin, Denis A.

doi:10.1210/jcem-69-4-716

Cited by 268 publications

(103 citation statements)

References 48 publications

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“…Similar results have been reported in human luteal cells, in which IGF-I enhances both basal and hCG-stimulated progesterone production (Devoto et al, 1995). In addition, IGF-I induces an increase in oestradiol secretion by human luteinized granulosa cells and by luteal cells in culture (Erickson et al, 1989;Johnson et al, 1996). These results indicate that IGF-I has a role in the regulation of the steroidogenic function of the human corpus luteum.…”

Section: Introductionsupporting

confidence: 71%

Effect of nitric oxide on the expression of insulin-like growth factors and the insulin-like growth factor binding proteins throughout the lifespan of the human corpus luteum

Iniguez¹

2001

Reproduction

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ResearchThe presence of insulin-like growth factors (IGF), IGF binding proteins (IGFBP) and IGF receptor type 1 (IGF-IR) in the human corpus luteum was investigated by examining the expression and production of related proteins throughout the lifespan of the corpus luteum and the action of nitric oxide upon their production. The expression of proteins in corpora lutea from the early, midand late luteal phases was assessed by immunohistochemistry, evaluated by a semi-quantitative analysis and the functional study was performed in corpus luteum explants incubated with nitric oxide donors. IGF-I and -II and IGFBP-1 and -3 were measured in the culture media by specific immunoassays. The results showed that IGF-I and -II, IGFBP-1 to -6 and IGF-IR were detected in the human corpus luteum throughout the luteal phase. Moreover, the expression and production of IGF-I and IGFBP-1 increased progressively from corpora lutea from the early to late luteal phases (P < 0.05), whereas the expression and production of IGFBP-2, -4 and -5 were significantly higher in corpora lutea from the mid-luteal phase (P < 0.05). No differences were observed in the expression of IGF-II, IGFBP-3 and -6 and IGF-IR throughout the lifespan of the corpus luteum. However, functional studies showed that nitric oxide donors elicited a stimulatory action on production of IGF-I in corpora lutea from the early luteal phase (80%) and on production of IGFBP-1 in corpora lutea from the late luteal phase (50%) (P < 0.05), whereas production of IGF-II and IGFBP-3 was not affected by nitric oxide. In conclusion, the components of the IGF-IGFBP system are expressed in the human corpus luteum throughout its lifespan. Nitric oxide regulates IGF-I and IGFBP-1 production, indicating that the growth factors may serve, at least in part, as mediators of the action of nitric oxide in the human corpus luteum.

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Section: Introductionsupporting

confidence: 71%

Effect of nitric oxide on the expression of insulin-like growth factors and the insulin-like growth factor binding proteins throughout the lifespan of the human corpus luteum

Iniguez¹

2001

Reproduction

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“…In human granulosa cells, however, IGF-I alone increases estradiol production to levels comparable to those induced by FSH, although together these hormones also have a synergistic effect [47][48][49].…”

Section: 3a Factors Affecting Aromatase Expression In Granulosa Cellsmentioning

confidence: 95%

Aromatase expression in the ovary: Hormonal and molecular regulation

2008

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Summary-Estrogens are synthesized by the aromatase enzyme encoded by the Cyp19a1 gene, which contains an unusually large regulatory region. In most mammals, aromatase expression is under the control of two distinct promoters a gonad-and a brain-specific promoter. In humans, this gene contains 10 tissue-specific promoters that are alternatively used in various cell types and tumors. Each promoter is regulated by a distinct set of regulatory sequences and transcription factors that bind to these specific sequences. The cAMP/PKA/CREB pathway is considered to be the primary signaling cascade through which the gonad Cyp19 promoter is regulated. Very interestingly, in rat luteal cells, the proximal promoter is not controlled in a cAMP dependent manner. Strikingly, these cells express aromatase at high levels similar to those found in preovulatory follicles, suggesting that alternative and powerful mechanisms control aromatase expression in luteal cells and that the rat corpus luteum represents an important paradigm for understanding alternative controls of the aromatase gene. Here, the molecular and cellular mechanisms controlling the expression of the aromatase gene in granulosa and luteal cells are discussed.

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“…Among many factors, locally produced intraovarian insulin-like growth factors (IGFs) 1 and their binding proteins (IGFBPs) and the renin-angiotensin system (RAS) have been shown to play important roles in the control of folliculogenesis and ovulation (1,(3)(4)(5)(6)(7). IGFs as well as IGFBPs are produced by ovarian granulosa cells (4,5,8).…”

Section: Introductionmentioning

confidence: 99%

Interactions between insulin-like growth factor-I (IGF-I) and the renin-angiotensin system in follicular growth and ovulation.

Yoshimura¹,

Aoki²,

Sueoka³

et al. 1996

J. Clin. Invest.

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The interactions between insulin-like growth factor-I (IGF-I) and the renin-angiotensin system (RAS) in follicular growth and ovulation were studied with the use of an isolated perfused rabbit ovary preparation. Ovulation failed to occur in either control ovaries or the experimental ovaries perfused with IGF-I in a concentration of 1, 10, or 100 ng/ml in the absence of gonadotropin. Exposure to IGF-I stimulated the secretion rate of angiotensin II-like immunoreactivity (Ang II-IR) in perfused rabbit ovaries in a dose-dependent manner. The percent increase in follicle diameter in ovaries perfused with IGF-I for 12 h was significantly correlated with the secretion rate of Ang II-IR at 12 h after exposure to IGF-I. The addition of IGFBP-3 to the perfusate did not induce ovulation in the absence of gonadotropin, but exposure to IGFBP-3 inhibited hCG-induced ovulation in a dosedependent manner. In addition, IGFBP-3 significantly reduced the ovarian secretion rate of Ang II-IR and prostaglandins stimulated by hCG administration. Intrafollicular plasminogen activator (PA) activity significantly increased within 4 h after exposure to 100 ng/ml of IGF-I, compared with that in control ovaries perfused with medium alone. The concomitant addition of IGFBP-3 to the perfusate significantly reduced the IGF-I-stimulated PA activity in the preovulatory follicles at 4, 6, and 8 h after exposure to IGF-I. However, IGFBP-3 alone affected neither the ovarian secretion rate of Ang II-IR nor intrafollicular PA activity. Exposure to streptokinase, an exogenous PA, in vitro stimulated both follicular growth and the intrafollicular Ang II-IR content. In conclusion, IGF-I enhances both ovarian Ang II production and follicular development by stimulating intrafollicular PA activity. ( J. Clin. Invest. 1996. 98:308-316.)

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Insulin-Like Growth Factor-I Regulates Aromatase Activity in Human Granulosa and Granulosa Luteal Cells*

Cited by 268 publications

References 48 publications

Effect of nitric oxide on the expression of insulin-like growth factors and the insulin-like growth factor binding proteins throughout the lifespan of the human corpus luteum

Effect of nitric oxide on the expression of insulin-like growth factors and the insulin-like growth factor binding proteins throughout the lifespan of the human corpus luteum

Aromatase expression in the ovary: Hormonal and molecular regulation

Interactions between insulin-like growth factor-I (IGF-I) and the renin-angiotensin system in follicular growth and ovulation.

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