Estrogen enhances growth hormone receptor expression and growth hormone action in rat osteosarcoma cells and human osteoblast-like cells

Postmenopausal bone loss is primarily due to estrogen deficiency. Recent clinical observation demonstrate that GH increases bone mass in GH deficient patients. The present study investigates whether estrogen regulates GH action and GH receptor expression in osteoblasts. 17 beta-estradiol or GH added to the culture medium as single substances did not influence rat osteosarcoma cell proliferation nor human osteoblast-like (hOB) cell proliferation. However, together they synergistically induced osteoblast proliferation (rat osteosarcoma cells 160.1 +/- 15.5% of control cells; human osteoblast-like cells 159.6 +/- 5.1% of control cells). 17 beta-estradiol stimulated 125I-GH binding and GH receptor (GHR) mRNA levels in rat osteosarcoma cells. The stimulatory effect of estradiol was time dependent, reaching a peak after 8 h of incubation with 17 beta-estradiol (binding 216.9 +/- 27.8% and mRNA 374.6 +/- 30.8% of control). The finding that estradiol stimulated 125I-GH binding was confirmed in human osteoblast-like cells. In these cells, 17 beta-estradiol (10(-12) M) increased 125I-GH binding to 203.8 +/- 3.6% of control levels. We conclude that estrogen stimulates GH activity as well as GH binding and GHR mRNA levels in osteoblasts. These findings indicate that estrogen potentiates the effect of GH at the receptor level.

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Developmental changes and differential regulation by testosterone and estradiol of growth hormone receptor expression in the rabbit

Acta Endocrinologica ◽

10.1530/eje.0.1350583 ◽

1996 ◽

Vol 135 (5) ◽

pp. 583-590 ◽

Cited By ~ 14

Author(s):

Yu M Yu ◽

Horacio M Domené ◽

Jorge Sztein ◽

Debra R Counts ◽

Fernando Cassorla

Keyword(s):

Growth Hormone ◽

Hormone Receptor ◽

Growth Hormone Receptor ◽

Treated Group ◽

Differential Regulation ◽

Receptor Expression ◽

Developmental Changes ◽

Mrna Levels ◽

R Gene ◽

Hormone Receptor Expression

Yu YM, Domené HM, Sztein J, Counts DR, Cassorla F. Developmental changes and differential regulation by testosterone and estradiol of growth hormone receptor expression in the rabbit. Eur J Endocrinol 1996;135:583–90. ISSN 0804–4643 To investigate the effects of testosterone and estradiol (E2) on growth hormone receptor (GH-R) gene expression, we measured GH-R mRNA levels in relation to the changes of sex steroid concentrations in the normal male rabbits aged 1–12 months and after administration of testosterone or E2 to castrated male rabbits. In the normal animals, E2 levels were below the detection limit in all age groups, and testosterone levels were below the detection limit at 1 month, increased at 2 months and reached the plateau of the adult levels after 4 months. Liver GH-R mRNA levels were low at 1 month, reached a peak at 2 months and then decreased slightly thereafter. In the castrated animals, liver and growth plate GH-R mRNA levels were increased in the testosterone-treated group (162.0 ± 12.0%, p < 0.025; 128.4 ± 7.6%; p < 0.025) and reduced in the E2-treated group (29.6 ± 6.2%, p < 0.005; 53.6 ± 11.3%, p < 0.025). Sex steroid administration did not result in any significant change in GH-R mRNA levels in striated muscle, kidney and heart. Serum GH concentrations were increased in E2 (15.3 ± 7.7 μg/l vs 4.8 ± 2.2 μg/l, p < 0.025) but the increase was not significant in testosterone-treated animals (8.4 ± 7.7 μg/l vs 4.8 ± 2.2 μg/l). Both testosterone and E2 treatment resulted in a reduction of mean serum growth hormone-binding protein (GHBP) levels compared to control animals (1077 ± 422 pmol/l, p < 0.01; 1137 ± 443 pmol/l, p < 0.01; 2308 ± 565 pmol/l). We conclude that in addition to their stimulatory effect on GH secretion, testosterone and E2 have opposite effects on GH-R gene expression in liver and growth plate in the rabbit. The modulation of GH-R expression by sex steroids may be important for growth during sexual maturation in mammals. Yu M Yu, MD, 11600 Bootjack Court, Gaithersburg, MD 20878, USA

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Cortisol increases growth hormone-receptor expression in human osteoblast-like cells

Journal of Endocrinology ◽

10.1677/joe.0.1560099 ◽

1998 ◽

Vol 156 (1) ◽

pp. 99-105 ◽

Cited By ~ 10

Author(s):

D Swolin-Eide ◽

A Nilsson ◽

C Ohlsson

Keyword(s):

Growth Hormone ◽

Control Culture ◽

Receptor Expression ◽

Serum Starvation ◽

Maximal Effect ◽

Mrna Levels ◽

Dependent Manner ◽

Human Osteoblast ◽

Receptor Mrna ◽

Gh Receptor

It is well known that high levels of glucocorticoids cause osteoporosis and that physiologic levels of growth hormone (GH) are required for normal bone remodeling. It has been suggested that glucocorticoids regulate GH-responses via the regulation of GH-receptor expression. The aim of the present study was to investigate whether cortisol plays a role in the regulation of GH-receptor expression in cultured human osteoblasts. The effect of serum starvation and cortisol on GH-receptor expression was tested in human osteoblast (hOB)-like cells. Serum starvation for 24 h resulted in an increase in GH-receptor mRNA levels (90 +/- 1% over control culture). Cortisol increased GH-receptor mRNA levels in a dose-dependent manner with a maximal effect at 10(-6)M. The stimulating effect of cortisol on GH-receptor mRNA levels was time-dependent, reaching a peak 12 h after the addition of cortisol (126 +/- 29% over control culture) and remaining up to 12 h later. The increase in GH-receptor mRNA levels was accompanied by an increase in 125I-GH binding which reached a maximum at 24 h (196 +/- 87% over control culture). In conclusion, glucocorticoids increase GH-receptor expression in hOB-like cells. Further studies are needed to clarify whether glucocorticoid-induced regulation of the GH-receptor is important in human bone physiology.

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Growth Hormone Receptor Expression in the Rat Gastrointestinal Tract*

Endocrinology ◽

10.1210/endo-126-1-299 ◽

1990 ◽

Vol 126 (1) ◽

pp. 299-306 ◽

Cited By ~ 86

Author(s):

PETER E. LOBIE ◽

WINRICH BREIPOHL ◽

MICHAEL J. WATERS

Keyword(s):

Growth Hormone ◽

Gastrointestinal Tract ◽

Hormone Receptor ◽

Growth Hormone Receptor ◽

Receptor Expression ◽

Hormone Receptor Expression

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Cortical ablation induces time-dependent changes in rat pituitary somatotrophs and upregulates growth hormone receptor expression in the injured cortex

Journal of Neuroscience Research ◽

10.1002/jnr.23408 ◽

2014 ◽

Vol 92 (10) ◽

pp. 1338-1349 ◽

Cited By ~ 2

Author(s):

Irena Lavrnja ◽

Vladimir Ajdzanovic ◽

Svetlana Trifunovic ◽

Danijela Savic ◽

Verica Milosevic ◽

...

Keyword(s):

Growth Hormone ◽

Hormone Receptor ◽

Growth Hormone Receptor ◽

Receptor Expression ◽

Time Dependent ◽

Cortical Ablation ◽

Rat Pituitary ◽

Hormone Receptor Expression

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Heterogeneity of Growth Hormone Receptor Expression in Craniopharyngioma—Implications for Surgical Strategy

World Neurosurgery ◽

10.1016/j.wneu.2020.02.022 ◽

2020 ◽

Vol 138 ◽

pp. 89-92

Author(s):

Yoshikazu Ogawa ◽

Masataka Kudo ◽

Mika Watanabe ◽

Teiji Tominaga

Keyword(s):

Growth Hormone ◽

Hormone Receptor ◽

Growth Hormone Receptor ◽

Receptor Expression ◽

Surgical Strategy ◽

Hormone Receptor Expression

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MiR-15a Decreases Bovine Mammary Epithelial Cell Viability and Lactation and Regulates Growth Hormone Receptor Expression

Molecules ◽

10.3390/molecules171012037 ◽

2012 ◽

Vol 17 (10) ◽

pp. 12037-12048 ◽

Cited By ~ 42

Author(s):

Hui-Ming Li ◽

Chun-Mei Wang ◽

Qing-Zhang Li ◽

Xue-Jun Gao

Keyword(s):

Growth Hormone ◽

Epithelial Cell ◽

Cell Viability ◽

Hormone Receptor ◽

Mammary Epithelial Cell ◽

Growth Hormone Receptor ◽

Mammary Epithelial ◽

Receptor Expression ◽

Bovine Mammary Epithelial Cell ◽

Hormone Receptor Expression

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Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/insulin-like growth factor system in adult mice

Journal of Endocrinology ◽

10.1677/joe.0.1670295 ◽

2000 ◽

Vol 167 (2) ◽

pp. 295-303 ◽

Cited By ~ 17

Author(s):

JW van Neck ◽

NF Dits ◽

V Cingel ◽

IA Hoppenbrouwers ◽

SL Drop ◽

...

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Receptor Antagonist ◽

Growth Hormone Receptor ◽

Binding Protein ◽

Mrna Levels ◽

Insulin Like Growth Factor ◽

Gh Receptor ◽

Igf I ◽

Igfbp 3

The effects of growth hormone (GH) in regulating the expression of the hepatic and renal GH and insulin-like growth factor (IGF) system were studied by administering a novel GH receptor antagonist (GHRA) (B2036-PEG) at different doses (0, 1.25, 2.5, 5 and 10 mg/kg/day) to mice for 7 days. No differences were observed in the groups with respect to body weight, food consumption or blood glucose. However, a dose-dependent decrease was observed in circulating IGF-I levels and in hepatic and renal IGF-I levels at the highest doses. In contrast, in the 5 and 10 mg/kg/day GHRA groups, circulating and hepatic transcriptional IGF binding protein-3 (IGFBP-3) levels were not modified, likely resulting in a significantly decreased IGF-I/IGFBP-3 ratio. Hepatic GH receptor (GHR) and GH binding protein (GHBP) mRNA levels increased significantly in all GHRA dosage groups. Endogenous circulatory GH levels increased significantly in the 2.5 and 5 mg/kg/day GHRA groups. Remarkably, increased circulating IGFBP-4 and hepatic IGFBP-4 mRNA levels were observed in all GHRA administration groups. Renal GHR and GHBP mRNA levels were not modified by GHRA administration at the highest doses. Also, renal IGFBP-3 mRNA levels remained unchanged in most GHRA administration groups, whereas IGFBP-1, -4 and -5 mRNA levels were significantly increased in the 5 and 10 mg/kg/day GHRA administration groups. In conclusion, the effects of a specific GHR blockade on circulating, hepatic and renal GH/IGF axis reported here, may prove useful in the future clinical use of GHRAs.

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