Differential Expression of Estrogen Receptor-  (ER ) in Human Pituitary Tumors: Functional Interactions with ER  and a Tumor-Specific Splice Variant

Chaidarun, Sushela

doi:10.1210/jc.83.9.3308

Cited by 32 publications

(33 citation statements)

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“…Even though expression of alpha-, beta-and splice variant isoforms of estrogen receptors has been shown in different proportions in the different types of pituitary tumors (17,18), the lack of change in GH levels in our series rules out a central action at the pituitary or hypothalamic level.…”

Section: Discussionmentioning

confidence: 64%

Raloxifene lowers IGF-I levels in acromegalic women

Attanasio

Barausse

Cozzi

2003

European Journal of Endocrinology

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Background: IGF-I suppression in acromegaly obtained by tamoxifen, a selective estrogen receptor modulator (SERM), prompted us to evaluate the effects of the administration of a newer SERM, raloxifene (RAL), devoid of estrogenic activity at uterine level, on GH/IGF-I levels in patients with this disease. Patients: Thirteen post-menopausal acromegalic women (aged 55-84 years) with active acromegaly entered a prospective open pilot study of RAL treatment at 60 mg/day. Nine of the patients, who were resistant to somatostatin analog and dopamine agonist treatment, were not undertaking therapy; the other four, who were partially sensitive to medical treatment, maintained treatment at the maximally effective dosages throughout the study. Results: IGF-I levels fell significantly from 444 (median, interquartile 393-590) mg/l to 300 (216 -608) mg/l ðP ¼ 0:0192Þ after 1 month of RAL administration and this fall remained stable up to the final evaluation at 5^1 months from the start of RAL treatment (260 (187-410) mg/l). An IGF-I decrease greater than 30% of basal values was observed in 10 patients (mainly in patients with IGF-I levels lower than 600 mg/l) and normal values were reached in seven (54%). GH levels did not change (basal 6 (4.1 -8) mg/l, final 5.5 (3.2-7.4) mg/l). The clinical picture improved in patients sensitive to RAL. RAL withdrawal was followed by the return of IGF-I levels to pretreatment values within 8 weeks in all patients. Conclusions: RAL decreases IGF-I levels in most acromegalic women with mild or intermediate disease (i.e. with values lower than 600 mg/l) and normalizes it in many. A prospective randomized study in patients resistant or partially sensitive to other medical treatments is warranted.

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Section: Discussionmentioning

confidence: 64%

Raloxifene lowers IGF-I levels in acromegalic women

Attanasio

Barausse

Cozzi

2003

European Journal of Endocrinology

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“…This consideration arises because ER␤ is upregulated by depletion of ER␣ in some systems, and exerts countervailing transcriptional effects on certain gene promotors (21,34,35). The notion is consistent with the fact that both ER␣ and ER␤ are expressed in the human pituitary gland (6,39).…”

Section: Discussionmentioning

confidence: 68%

Peripheral estrogen receptor-α selectively modulates the waveform of GH secretory bursts in healthy women

Veldhuis¹,

Keenan²,

Bowers³

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Veldhuis JD, Keenan DM, Bowers CY. Peripheral estrogen receptor-␣ selectively modulates the waveform of GH secretory bursts in healthy women. Am J Physiol Regul Integr Comp Physiol 293: R1514-R1521, 2007. First published August 8, 2007; doi:10.1152 doi:10. /ajpregu.00438.2007 drives growth hormone (GH) secretion via estrogen receptors (ER) located in the hypothalamus and pituitary gland. ER␣ is expressed in GH releasing hormone (GHRH) neurons and GH-secreting cells (somatotropes). Moreover, estrogen regulates receptors for somatostatin, GHR peptide (GHRP, ghrelin), and GH itself, while potentiating signaling by IGF-I. Given this complex network, one cannot a priori predict the selective roles of hypothalamic compared with pituitary ER pathways. To make such a distinction, we introduce an investigative model comprising 1) specific ER␣ blockade with a pure antiestrogen, fulvestrant, that does not penetrate the blood-brain barrier; 2) graded transdermal E 2 administration, which doubles GH concentrations in postmenopausal women; 3) stimulation of fasting GH secretion by pairs of GHRH, GHRP-2 (a ghrelin analog), and L-arginine (to putatively limit somatostatin outflow); and 4) implementation of a flexible waveform deconvolution model to estimate the shape of secretory bursts independently of their size. The combined strategy unveiled that 1) E 2 prolongs GH secretory bursts via fulvestrant-antagonizable mechanisms; 2) fulvestrant extends GHRH/GHRP-2-stimulated secretory bursts; 3) L-arginine/GHRP-2 stimulation lengthens GH secretory bursts whether or not E 2 is present; 4) E2 limits the capability of L-arginine/GHRP-2 to expand GH secretory bursts, and fulvestrant does not inhibit this effect; and 5) E 2 and/or fulvestrant do not alter the time evolution of L-arginine/GHRH-induced GH secretory bursts. The collective data indicate that peripheral ER␣-dependent mechanisms determine the shape (waveform) of in vivo GH secretory bursts and that such mechanisms operate with secretagogue selectivity. somatotropin; ghrelin; growth hormone releasing hormone; somatostatin; secretagogues; female; human GROWTH HORMONE (GH) secretion is at least 90% pulsatile in the healthy human and strongly controlled by sex steroid hormones (17,19). Individual GH secretory bursts are believed to reflect the concerted effects of somatotrope stimulation by GH-releasing hormone (GHRH), inhibition by somatostatin (SS), and amplification by the potent GHR peptide (GHRP) ghrelin (14,45). Estrogen supplementation stimulates pulsatile GH secretion in postmenopausal women and girls with ovarian dysgenesis (32, 38). Putative mechanisms include the capability of estradiol (E 2 ) to potentiate GHRH drive (reduce the halfmaximally stimulatory dose), augment GHRP stimulation (increase apparent efficacy), and antagonize SS inhibition (increase the half-maximally inhibitory dose) (2, 5, 41, 43). The topographic sites at which estrogen exerts such effects are not known (45). However, E 2 can upregulate pituitary SS-type 2 and hypothalamic GHRP receptors and...

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“…We first assessed the levels of NM23-H1 and NM23-H2 expressed in a number of cultured cell lines that have been used to study estrogen responsiveness (13,14,23,24). MCF-7 breast cancer, U2OS, and HeLa cervical cancer cells expressed higher levels of NM23-H1 and NM23-H2 than MDA-MB-231 breast cancer cells, but only MCF-7 cells expressed ERa (Fig.…”

Section: Resultsmentioning

confidence: 99%

Interaction of the Tumor Metastasis Suppressor Nonmetastatic Protein 23 Homologue H1 and Estrogen Receptor α Alters Estrogen-Responsive Gene Expression

et al. 2007

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Metastasis of cancer cells from the primary tumor is associated with poor prognosis and decreased overall survival. One protein implicated in inhibiting metastasis is the tumor metastasis suppressor nonmetastatic protein 23 homologue 1 (NM23-H1). NM23-H1 is a multifunctional protein, which, in addition to limiting metastasis, has DNase and histidine protein kinase activities. We have identified new functions for NM23-H1 in influencing estrogen receptor A (ERA)-mediated gene expression. Using a battery of molecular and biochemical techniques, we show that NM23-H1 interacts with ERA and increases the ERA-estrogen response element (ERE) interaction. When NM23-H1 expression is increased in U2 osteosarcoma and MDA-MB-231 breast cancer cells, transcription of a transiently transfected, estrogen-responsive reporter plasmid is decreased. More importantly, when endogenous NM23-H1 expression is knocked down in MCF-7 human breast cancer cells using small interfering RNA, estrogen responsiveness of the progesterone receptor (PR), Bcl-2, cathepsin D, and cyclin D1 genes, but not the pS2 gene, is enhanced. Furthermore, NM23-H1 associates with the region of the PR gene containing the +90 activator protein 1 site, but not with the ERE-containing region of the pS2 gene, indicating that NM23-H1 mediates gene-specific effects by association with endogenous chromatin. Our studies suggest that the capacity of NM23-H1 to limit the expression of estrogen-responsive genes such as cathepsin D and Bcl-2, which are involved in cell migration, apoptosis, and angiogenesis, may help to explain the metastasis-suppressive effects of this protein. The complementary abilities of ERA and NM23-H1 together to influence gene expression, cell migration, and apoptosis could be key factors in helping to determine tumor cell fate. [Cancer Res 2007;67(21):10600-7]

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Differential Expression of Estrogen Receptor- (ER ) in Human Pituitary Tumors: Functional Interactions with ER and a Tumor-Specific Splice Variant

Cited by 32 publications

References 0 publications

Raloxifene lowers IGF-I levels in acromegalic women

Raloxifene lowers IGF-I levels in acromegalic women

Peripheral estrogen receptor-α selectively modulates the waveform of GH secretory bursts in healthy women

Interaction of the Tumor Metastasis Suppressor Nonmetastatic Protein 23 Homologue H1 and Estrogen Receptor α Alters Estrogen-Responsive Gene Expression

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