Effects of the selective estrogen receptor modulator LY117018 on growth hormone secretion: in vitro studies

Tulipano, Giovanni; Bonfanti, Carlo; Poiesi, Claudio; Burattin, Anna; Turazzi, S.; Barone, G.; Cozzi, Renato; Bollati, A; Valle, Domenico; Giustina, Andrea

doi:10.1016/j.metabol.2003.12.004

Cited by 10 publications

(12 citation statements)

References 32 publications

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“…These data correlate well with those previous in vitro and in vivo studies that used relatively low concentrations of estrogen to show its enhancing effects on somatotropes (Bethea, 1991;Webb et al, 1983;Simard et al, 1986;Lam et al, 1996;Tulipano et al, 2004). However, those studies that used concentrations of 10 nM or greater most often reported no effects, or even inhibitory effects of estrogen (Fukata and Martin, 1986;Silverman et al, 1988;Hauspie et al, 2003).…”

supporting

confidence: 89%

“…First, there has been controversy about the presence or types of estrogen receptors on somatotropes (Kikuta et al, 1993;Friend et al, 1994;Shupnik, 2002;Stefanneau et al, 1994;Zafer et al, 1995;Chaidarun et al, 1997;Chaidarun et al,m 1998;Gittoes et al, 1999;Shupnik et al1998;Hal and McDonnell, 1999). Second, not all in vitro studies have demonstrated an estrogen-mediated increase in GH synthesis or secretion (Webb et al, 1983;Simard et al, 1985;Lam et al, 1996;Tulipano et al, 2004;Fukuta and Martin, 1986;Silverman et al, 1988;Hauspie et al, 2003.). In some studies, estrogen has had no effects or inhibitory effects on expression of GH (Fukuta and Martin, 1986;Silverman et al, 1988;Hauspie et al, 2003.…”

mentioning

confidence: 99%

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Estrogen mediated cross talk between the ovary and pituitary somatotrope

Childs

Iruthayanathan

Akhter

et al. 2006

Molecular and Cellular Endocrinology

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supporting

confidence: 89%

mentioning

confidence: 99%

Estrogen mediated cross talk between the ovary and pituitary somatotrope

Childs

Iruthayanathan

Akhter

et al. 2006

Molecular and Cellular Endocrinology

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“…However, on the somatotropic axis, the anti-estrogenic actions were different from that on the gonadotropic axis. Treatment with anti-estrogen increased serum levels of GH, and decreased that of IGF-I (Bellantoni et al 1996;Oleksik et al 2001;Tulipano et al 2004). In fish, anti-estrogens (ICI 182780 and TCDD) were also reported to increase the expression of GH as well as possessing estrogen-like activities (Elango et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Disrupting actions of bisphenol A and malachite green on growth hormone receptor gene expression and signal transduction in seabream

Jiao

Chen

2008

Fish Physiol Biochem

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Environmental estrogen could mimic natural estrogens thereby disrupting the endocrine systems of human and animals. The actions of such endocrine disruptors have been studied mainly on reproduction and development. However, estrogen could also affect the somatotropic axis via multiple targets such as growth hormone (GH). In the present study, two endocrine disruptors were chosen to investigate their effects on the expression level and signal transduction of growth hormone receptor (GHR) in fish. Using real-time PCR, it was found that exposure to both the estrogenic (bisphenol A) and anti-estrogenic (malachite green) compounds could attenuate the expression levels of GHR1 and GHR2 in black seabream (Acanthopagrus schlegeli) hepatocytes. The expression level of IGF-I, the downstream effector of GHR activation in the liver, was decreased by bisphenol A but not by malachite green. Luciferase reporter assay of the beta-casein promoter was used to monitor GHR signaling in transfected cells. In the fish liver cell line Hepa-T1, both GHR1 and GHR2 signaling were attenuated by bisphenol A and malachite green. This attenuation could only occur in the presence of estrogen receptor, indicating that these agents probably produce their actions via the estrogen receptor. Results of the present study demonstrated that estrogenic or anti-estrogenic compounds could down-regulate the somatotropic axis in fish by affecting both the gene expression and signaling of GHR. In view of the increasing prevalence of these compounds in the environment, the impact on fish growth and development both in the wild and in aquaculture would be considerable.

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“…Previous studies have indicated that E2 is a critical factor in the regulation of many pituitary hormones [42] and that it can influence both hormone synthesis and secretion [12]. As such, E2 performs a pivotal role in human growth, since it stimulates growth by increasing secretion of pituitary GH and exerting a direct effect on the growth plates [5].…”

Section: Effect Of Endocrine Disruptor On Induction Of Gh Expressionmentioning

confidence: 99%

“…In humans, the physiological effects of estrogens on the pituitary gland have been well documented [12], and E2 has been shown to exert its biological effects via the hypothalamic-pituitary axis, modulating expression and release of anterior pituitary hormones such as GH and PRL [13,14]. In rat anterior pituitary cells, E2 stimulates synthesis and release of GH [15], and the estrogen receptor (ER) signaling pathway mediates E2-induced cellular responses such as proliferation and regulation of hormone synthesis [16].…”

mentioning

confidence: 99%

Estrogen Receptors are Involved in Xenoestrogen Induction of Growth Hormone in the Rat Pituitary Gland

Dang

Choi

Jeung

2009

Journal of Reproduction and Development

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Abstract. Growth hormone (GH) plays a pivotal role in the regulation of growth, development and body composition. In order to provide new insights into estrogenic endocrine disruptor (ED) activities in the pituitary gland and the potential role played by estrogen receptors (ERs) in mediating their effects in vivo, we examined GH expression in the pituitary gland of an immature rat model. At postnatal day 14, immature rats were treated with various doses of 4-tertoctylphenol (OP), p-nonylphenol (NP) and bisphenol A (BPA), and the GH mRNA and protein expression levels were analyzed by real-time quantitative PCR and western blot/immunohistochemistry (IHC), respectively. An anti-estrogen (ICI 182780) was used to examine the potential involvement of ERs in ED-induced GH expression during critical windows of development. GH mRNA expression increased significantly 48 h after treatment with a high dose (600 mg/ kg body weight [BW]) of OP or NP. However, this induction was abolished completely by co-treatment with ICI 182780. No significant difference in GH mRNA expression was observed following treatment with BPA or co-treatment of BPA with the anti-estrogen. Exposure to high doses (600 mg/kg BW) of these EDs significantly enhanced GH protein expression in the rat pituitary gland, whereas pretreatment with ICI 182780 markedly reduced this expression. Taken together, we have demonstrated for the first time that in vivo exposure to EDs can induce GH mRNA and protein expression in the rat pituitary gland and that their activities may involve an ER-mediated signaling pathway. These results may provide critical evidence for ED-induced dysregulation of pituitary GH expression and thus may be important for elucidating the potential impacts of EDs in altered body growth and development and for predicting the health risks of ED exposure in humans and wildlife. Key words: Endocrine disruptor, Estrogenicity, Growth hormone, Pituitary gland, Rat (J. Reprod. Dev. 55: [206][207][208][209][210][211][212][213] 2009) rowth hormone (GH) plays a pivotal role in growth and development during puberty and is a member of a family of evolutionarily-related hormones that include prolactin (PRL) and placental lactogen [1]. In addition, GH performs important functions in metabolism and body composition [2]. GH activity can be regulated directly via sex steroids, which control GH release, or indirectly by modulation of insulin-like growth factor (IGF)-I [3]. Although most of its growth-promoting activity is mediated by IGF-I activation [1], studies have indicated that changes in circulating levels of sex steroids may lead to modulation of GH synthesis and release of GH from the anterior lobe of the pituitary [4]. In humans, GH regulates growth in childhood [5], and most endocrine disorders that influence body growth and development affect GH levels during this critical window. Recent reports have indicated a positive correlation between GH and estrogen levels in prepubertal girls and boys [6,7]. The effects of estrogen stimulation on growth dep...

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Effects of the selective estrogen receptor modulator LY117018 on growth hormone secretion: in vitro studies

Cited by 10 publications

References 32 publications

Estrogen mediated cross talk between the ovary and pituitary somatotrope

Estrogen mediated cross talk between the ovary and pituitary somatotrope

Disrupting actions of bisphenol A and malachite green on growth hormone receptor gene expression and signal transduction in seabream

Estrogen Receptors are Involved in Xenoestrogen Induction of Growth Hormone in the Rat Pituitary Gland

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