Modulation of anterior pituitary luteinizing hormone response to gonadotropin-releasing hormone by insulin-like growth factor I in vitro

Soldani, R; Cagnacci, Angelo; Paoletti, Anna Maria; Yen, S. S. C.; Melis, Gian Benedetto

doi:10.1016/s0015-0282(16)57804-2

Cited by 66 publications

(41 citation statements)

References 18 publications

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“…Metformin and the other insulin sensitizing agents interact on different levels of insulin physiology. Since these drugs act via different mechanisms, it has been suggested that the reduction of insulin may reduce directly or through unknown mechanisms, the pituitary LH synthesis and discharge [51,52], whereas orlistat acts indirectly through reduction of weight. It seems that longer treatment with orlistat is needed to reach a significant reduction in serum LH level.…”

Section: Discussionmentioning

confidence: 99%

The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study

Ghandi

Aflatoonian

Tabibnejad

et al. 2011

J Assist Reprod Genet

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Purpose Comparing the effects of metformin or orlistat on hormone, lipid profile and ovulation status in obese women with polycystic ovary syndrome. Methods A total of 80 women were prospectively recruited to receive either metformin (n=40) or orlistat (n=40). Weight, BMI, waist, serum LH, total serum testosterone and lipid profile were assessed at baseline and after 3 months. The subjects' ovulatory status was assessed after 3 months. Results There was no significant difference in ovulation between the two treatment groups (30% vs 15%). Treatment with either drug showed a significant decline in body weight, BMI (Body Mass Index), and waist circumference, but the degree of decline in both groups was the same. Patients who were treated with orlistat, showed a significant reduction in total testosterone and serum lipid. Women in metformin group showed a significant reduction in serum LH.Conclusions Both metformin and orlistat showed a similar effect on weight loss and ovulation rates.

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Section: Discussionmentioning

confidence: 99%

The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study

Ghandi

Aflatoonian

Tabibnejad

et al. 2011

J Assist Reprod Genet

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“…For example, intraventricular administration of IGF-I in female rats increased plasma luteinizing hormone (LH) and advanced the onset of puberty (Hiney et al, 1996). The administration of IGF-I to rat pituitary cell cultures increased basal secretion of follicle-stimulating hormone (FSH) and LH and gonadotropin-releasing hormone (GnRH)-induced LH secretion (Kanematsu, et al, 1991;Soldani et al, 1994Soldani et al, , 1995Xia et al, 2001). Moreover, in male rats, IGF-I stimulated release of FSH and LH, with increased expression of the glycoprotein α (GPα) subunit gene but not of the FSHβ, nor LHβ subunit genes (Pazos et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Molecular Regulation of Gonadotropin Secretion by Gonadotropin Releasing Hormone in Salmonid Fishes

Ando¹,

Urano

2005

Zoological Science

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“…Phosphorylation of CBP via insulin results in dissociation of CBP from the CREB-CBP-TORC2 complex, and in gonadotrophs, it results in recruitment to the Lhb promoter and activation of Lhb gene expression. We and others have shown that insulin can increase GNRH-mediated Lhb expression and secretion with some evidence of a costimulatory effect of insulin and GNRH in L␤T2 cells via activation of AKT and extracellular signal-regulated kinase (ERK) (1,4,10,31,40). This suggests that energy-homeostatic information can be integrated at the level of the pituitary gland, possibly through CBP, to modulate reproductive function.…”

Section: Discussionmentioning

confidence: 92%

“…It has been established that gonadotrophs express insulin receptors on the cell surface and that L␤T2 cells are able to bind insulin (4, 17). We and others have demonstrated that insulin augments GNRH-mediated Lhb expression and LH secretion primarily via induction of 4,40). Thus, CBP may function to integrate multiple inputs, repro-…”

mentioning

confidence: 94%

CREB Binding Protein (CBP) Activation Is Required for Luteinizing Hormone Beta Expression and Normal Fertility in Mice

Miller

Wolfe

et al. 2012

Molecular and Cellular Biology

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Normal function of the hypothalamic-pituitary-gonadal axis is dependent on gonadotropin-releasing hormone (GNRH)-stimulated synthesis and secretion of luteinizing hormone (LH) from the pituitary gonadotroph. While the transcriptional coactivator CREB binding protein (CBP) is known to interact with Egr-1, the major mediator of GNRH action on the Lhb gene, the role of CBP in Lhb gene expression has yet to be characterized. We show that in the L␤T2 gonadotroph cell line, overexpression of CBP augmented the response to GNRH and that knockdown of CBP eliminated GNRH responsiveness. While GNRH-mediated phosphorylation of CBP at Ser436 increased the interaction with Egr-1 on the Lhb promoter, loss of this phosphorylation site eliminated GNRH-mediated Lhb expression in L␤T2 cells. In vivo, loss of CBP phosphorylation at Ser436 rendered female mice subfertile. S436A knock-in mice had disrupted estrous cyclicity and reduced responsiveness to GNRH. Our results show that GNRHmediated phosphorylation of CBP at Ser436 is required for Egr-1 to activate Lhb expression and is a requirement for normal fertility in female mice. As CBP can be phosphorylated by other factors, such as insulin, our studies suggest that CBP may act as a key regulator of Lhb expression in the gonadotroph by integrating homeostatic information with GNRH signaling. Reproductive viability in humans is dependent on normal function of the hypothalamic-pituitary-gonadal axis. Gonadotropin-releasing hormone (GNRH) is produced by hypothalamic neurosecretory cells and released in a pulsatile manner into the hypothalamo-hypophyseal portal circulation, through which the hormone is transported to the anterior pituitary gland. GNRH bound to its receptor on pituitary gonadotrophs results in an increase in GNRH receptor density and stimulates the synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) into the circulation (14,30,41). LH and FSH are heterodimeric glycoproteins consisting of a common ␣-subunit and hormone-specific ␤-subunit encoded by the Lhb and Fshb genes, respectively. Lhb and Fshb gene expression in the anterior pituitary is dependent on pulsatile GNRH secretion. Rapid, highamplitude GNRH pulses stimulate an increase in Lhb mRNA levels, leading to an increase in LH synthesis and release from the gonadotroph (11,18,45,51).At least three major transcription factors are important for Lhb gene expression: steroidogenic factor 1 (SF-1), pituitary homeobox factor 1 (Pitx1), and early growth response factor 1 (Egr-1). GNRH stimulates the expression of Egr-1, resulting in Egr-1 binding to two conserved cis elements of the proximal Lhb promoter (5, 43, 49). Egr-1 is rapidly and markedly induced by GNRH, while SF-1 and Pitx1 expression levels are unchanged following GNRH administration (43, 49). In rat, Egr-1 expression increases in proestrous, suggesting that it may be an important signal for ovulation (39). Loss of Egr-1 in the gonadotroph, unlike loss of SF-1 or Pitx1, renders the cell unable to respond to GNRH, and Egr-1...

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Modulation of anterior pituitary luteinizing hormone response to gonadotropin-releasing hormone by insulin-like growth factor I in vitro

Cited by 66 publications

References 18 publications

The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study

The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open-label study

Molecular Regulation of Gonadotropin Secretion by Gonadotropin Releasing Hormone in Salmonid Fishes

CREB Binding Protein (CBP) Activation Is Required for Luteinizing Hormone Beta Expression and Normal Fertility in Mice

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