Follicle-stimulating hormone, interleukin-1, and bone density in adult women

Cannon, Joseph G.; Cortez‐Cooper, Miriam; Meaders, Eric; Stallings, Judith; Haddow, Sara; Kraj, Barbara; Sloan, Gloria; Mulloy, Anthony L.

doi:10.1152/ajpregu.00728.2009

Cited by 61 publications

(66 citation statements)

References 50 publications

(43 reference statements)

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“…Wu et al independently show that FSH stimulates osteoclastogenesis, which is abolished in mice lacking immunoreceptor tyrosine-based activation motif (ITAM) adapter signaling molecules (11). FSHR activation also enhances receptor activator of nuclear factor kappa-B (RANK) receptor expression (29), and indirectly stimulates osteoclast formation by releasing IL-1β, TNF-α, and IL-6 (30,31). Serum FSH levels thus correlate with circulating cytokine concentrations (32).…”

Section: Discussionmentioning

confidence: 99%

Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis

Zhu

Blair

Cao

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

139

143

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Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins 3 y before the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during late perimenopause, directly stimulates bone resorption by osteoclasts. Here, we generated and characterized a polyclonal antibody to a 13-amino-acid-long peptide sequence within the receptor-binding domain of the FSH β-subunit. We show that the FSH antibody binds FSH specifically and blocks its action on osteoclast formation in vitro. When injected into ovariectomized mice, the FSH antibody attenuates bone loss significantly not only by inhibiting bone resorption, but also by stimulating bone formation, a yet uncharacterized action of FSH that we report herein. Mesenchymal cells isolated from mice treated with the FSH antibody show greater osteoblast precursor colony counts, similarly to mesenchymal cells isolated from FSH receptor (FSHR) −/− mice. This suggests that FSH negatively regulates osteoblast number. We confirm that this action is mediated by signaling-efficient FSHRs present on mesenchymal stem cells. Overall, the data prompt the future development of an FSH-blocking agent as a means of uncoupling bone formation and bone resorption to a therapeutic advantage in humans.osteoporosis | sex steroids | skeletal anabolic | gonadotropin W omen lose over 3% of bone mass during late perimenopause at which time estrogen levels remain relatively unperturbed (1, 2). This bone loss begins 3 y before the last menstrual period (3), and arises from a profound elevation in bone resorption, which is not compensated by parallel increases in bone formation (4). Inhibiting bone resorption during this period with an anticatabolic agent, such as a bisphosphonate, selective estrogen receptor modulator, or estrogen itself, attenuates bone loss (5). However, estrogen use can be associated with increased breast cancer risk and designer estrogens have undesirable side effects. Further, growing concerns regarding oversuppression of bone turnover by bisphosphonates limit their use as early as perimenopause (5). The relatively small armamentarium for osteoporosis therapies, particularly for early and rapidly progressing bone loss, makes the advent of newer preventative strategies very desirable.A close examination of hormonal changes in women during late perimenopause shows that, whereas estrogen levels remain unperturbed, FSH levels have begun to rise, likely to compensate for failing ovaries (3). Strong correlations between rising serum FSH levels and bone loss have been documented, particularly in the Study of Women's Health Across Nations (SWAN) (2, 6). Furthermore, amenorrheic women with high FSH levels >35 IU/L display greater decrements in bone density than those with a mean FSH of ∼8 IU/L (7). Likewise, women having activating FSH receptor (FSHR) polymorphisms have a low bone mass and high bone turnover (8). Together, these findings suggest that a rising ...

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Section: Discussionmentioning

confidence: 99%

Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis

Zhu

Blair

Cao

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

139

143

View full text Add to dashboard Cite

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“…In a separate study, FSHR activation was shown to enhance RANK receptor expression [20]. In addition, FSH indirectly stimulates osteoclast formation by releasing osteoclastogenic cytokines, namely interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in proportion to the surface expression of FSHRs [9,21]. In a study of 36 women between the ages of 20 and 50 years, serum FSH concentrations correlated with circulating cytokine concentrations [21,22].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Pituitary-bone connection in skeletal regulation

Zaidi

Sun

Liu

et al. 2016

Hormone Molecular Biology and Clinical Investigation

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Pituitary hormones have traditionally been thought to exert specific, but limited function on target tissues. More recently, the discovery of these hormones and their receptors in organs such as the skeleton suggests that pituitary hormones have more ubiquitous functions. Here, we discuss the interaction of growth hormone (GH), follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin and arginine vasopressin (AVP) with bone. The direct skeletal action of pituitary hormones therefore provides new insights and therapeutic opportunities for metabolic bone diseases, prominently osteoporosis.

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“…Other factors playing a role in bone loss during the menopause transition includes follicle stimulating hormone (FSH) (Cannon et al, 2010). The study by Sowers et al (2010) revealed an increase in bone loss by 2 years before the final menstrual period despite normal ranges of estrogen at that period.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the height of premenopausal and postmenopausal women in Zaria, Nigeria

Achie¹,

Olorunshola²,

Mabrouk³

2014

J. Physiol. Pathophysiol.

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Excessive height loss in postmenopausal women (PMW) has been found to reflect low bone mass; an index helpful in predicting vertebral fractures. One hundred and sixty five women were recruited for the cross-sectional study comprising of 77 premenopausal women who served as control and 88 PMW who constituted the study group. The subjects were administered a questionnaire after obtaining informed consent. While their height, weight, waist circumference and serum testosterone levels were determined utilizing standard methods. The results were presented as mean ± SD, while data was analyzed with Student's t-test, one way ANOVA, and correlation for comparing association; p<0.05 was considered significant. The postmenopausal women had a significantly lower mean height (158.56 ± 7.02 cm) than the premenopausal women (162.25 ± 6.44 cm), p<0.001. There was a decrease in mean postmenopausal height with increasing duration of menopause, however, it was not statistically significant; 158.71 ± 7.32, 158.40 ± 7.34 and 158.41 ± 6.41 cm, respectively for women who were 1-5, 6 -10 and > 10 years postmenopausal. The age at menopause and the body mass index demonstrated a positive correlation with the height of the menopausal women. While the serum testosterone and the body mass of the postmenopausal women demonstrated a negative correlation with their age at menopause. It is concluded that the postmenopausal women had a significantly lower height than the premenopausal women (mean height difference of 3.69 cm) and were at risk of vertebral fractures; critical levels predictive for vertebral fractures range between 3 -6 cm losses in height. We recommend longitudinal studies to determine the prospective height loss across the menopause transition in Nigerian women and thus indicate the critical levels predictive for vertebral fractures for Nigerian menopausal women.

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Follicle-stimulating hormone, interleukin-1, and bone density in adult women

Cited by 61 publications

References 50 publications

Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis

Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis

Pituitary-bone connection in skeletal regulation

Evaluation of the height of premenopausal and postmenopausal women in Zaria, Nigeria

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