Ultrastructural immunolocalization of IGF-1 and insulin receptors in rat pituitary culture: evidence of a functional interaction between gonadotroph and lactotroph cells

Gutiérrez, Silvina; Mukdsi, Jorge Humberto; Aoki, Agustı́n; Torres, Alicia Inés; Soler, Aléjandro Peralta; Orgnero, Elsa Margarita

doi:10.1007/s00441-006-0283-4

Cited by 18 publications

(17 citation statements)

References 43 publications

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“…Additionally, the pituitary gonadotroph expresses insulin receptors (Gutierrez et al 2007, Soldani et al 1994). While most of the studies using the LβT2 model system have suggested an augmentation of Lhb expression there are some differences obtained by different groups that should be noted.…”

Section: Insulin Regulation Of Neuroendocrine Functionmentioning

confidence: 99%

The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1)

Wolfe

DiVall

2014

Frontiers in Neuroendocrinology

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The mammalian reproductive hormone axis regulates gonadal steroid hormone levels and gonadal function essential for reproduction. The neuroendocrine control of the axis integrates signals from a wide array of inputs. The regulatory pathways important for mediating these inputs have been the subject of numerous studies. One class of proteins that have been shown to mediate metabolic and growth signals to the CNS includes Insulin and IGF-1. These proteins are structurally related and can exert endocrine and growth factor like action via related receptor tyrosine kinases. The role that insulin and IGF-1 play in controlling the hypothalamus and pituitary and their role in regulating puberty and nutritional control of reproduction has been studied extensively. This review summarizes the in vitro and in vivo models that have been used to study these neuroendocrine structures and the influence of these growth factors on neuroendocrine control of reproduction.

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Section: Insulin Regulation Of Neuroendocrine Functionmentioning

confidence: 99%

The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1)

Wolfe

DiVall

2014

Frontiers in Neuroendocrinology

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“…In addition, a series of evidence obtained by in vitro studies has also verified the effects of insulin on the proliferation of neural tissues, as in an in vitro study, the proliferatory effects of insulin were determined in pituitary cell culture and it was reported that incubation with insulin causes the number of lactotroph cells which undergo mitosis to increase, and this insulin-induced increase in proliferation was abolished when it was coincubated with the receptor tyrosine kinase inhibitor "genistein." Since insulin has stimulatory effects on protein synthesis by gonadotroph cells, it has been suggested that insulin-induced increase in lactotroph proliferation may be meditated indirectly by factors which are synthesized by gonadotroph cells [234]. Insulin has also been shown to regulate the proliferation and differentiation of multipotent neural stem cells, such as hippocampal neural stem cells, as insulin withdrawal causes these cells to undergo nonapoptotic, autophagic cell death demonstrated by cell morphology, PI staining, and proliferation assay [235].…”

Section: Proliferationmentioning

confidence: 99%

Insulin in the Brain: Sources, Localization and Functions

et al. 2012

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Historically, insulin is best known for its role in peripheral glucose homeostasis, and insulin signaling in the brain has received less attention. Insulin-independent brain glucose uptake has been the main reason for considering the brain as an insulin-insensitive organ. However, recent findings showing a high concentration of insulin in brain extracts, and expression of insulin receptors (IRs) in central nervous system tissues have gathered considerable attention over the sources, localization, and functions of insulin in the brain. This review summarizes the current status of knowledge of the peripheral and central sources of insulin in the brain, site-specific expression of IRs, and also neurophysiological functions of insulin including the regulation of food intake, weight control, reproduction, and cognition and memory formation. This review also considers the neuromodulatory and neurotrophic effects of insulin, resulting in proliferation, differentiation, and neurite outgrowth, introducing insulin as an attractive tool for neuroprotection against apoptosis, oxidative stress, beta amyloid toxicity, and brain ischemia.

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“…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 Egr-1 (1,4,40).…”

mentioning

confidence: 77%

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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Ultrastructural immunolocalization of IGF-1 and insulin receptors in rat pituitary culture: evidence of a functional interaction between gonadotroph and lactotroph cells

Cited by 18 publications

References 43 publications

The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1)

The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1)

Insulin in the Brain: Sources, Localization and Functions

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

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