Effect of natural menopause on serum levels of IGF-I and IGF-binding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women

Nasu, M; Sugimoto, Toshitsugu; Chihara, Mieko; Hiraumi, Mitsuo; Kurimoto, Fumihiko; Chihara, Kazuo

doi:10.1530/eje.0.1360608

Cited by 57 publications

(26 citation statements)

References 36 publications

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“…Blood levels of growth hormone, IGF-I and prolactin also decline with increasing age (Hall et al, 1999). Prolactin levels are also permanently reduced by pregnancy, and are lower after the menopause than before (Reyes et al, 1977;Wang et al, 1988;Metka et al, 1995;Nasu et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

The association of breast mitogens with mammographic densities

et al. 2002

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Radiologically dense breast tissue (mammographic density) is strongly associated with risk of breast cancer, but the biological basis for this association is unknown. In this study we have examined the association of circulating levels of hormones and growth factors with mammographic density. A total of 382 subjects, 193 premenopausal and 189 postmenopausal, without previous breast cancer or current hormone use, were selected in each of five categories of breast density from mammography units. Risk factor information, anthropometric measures, and blood samples were obtained, and oestradiol, progesterone, sex hormone binding globulin, growth hormone, insulin-like growth factor-I and its principal binding protein, and prolactin measured. Mammograms were digitised and measured using a computer-assisted method. After adjustment for other risk factors, we found in premenopausal women that serum insulin-like growth factor-I levels, and in postmenopausal women, serum levels of prolactin, were both significantly and positively associated with per cent density. Total oestradiol and progesterone levels were unrelated to per cent density in both groups. In postmenopausal women, free oestradiol (negatively), and sex hormone binding globulin (positively), were significantly related to per cent density. These data show an association between blood levels of breast mitogens and mammographic density, and suggest a biological basis for the associated risk of breast cancer.

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Section: Discussionmentioning

confidence: 99%

The association of breast mitogens with mammographic densities

et al. 2002

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“…Indeed, our clinical studies showed that the suppression of the GH-insulin-like growth factor-I (IGF-I) axis was partly associated with age-dependent bone loss as well as bone loss after gonadal failure [5,6]. The adult skeleton is cycli cally remodelled by osteoclastic bone resorption followed by osteoblastic bone formation -the cavities excavated by osteoclasts are subsequently refilled by osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

The Action of GH/IGF-I/IGFBP in Osteoblasts and Osteoclasts

Chihara

Sugimoto²

1997

Horm Res

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Bone remodelling is a cyclical phenomenon consisting of osteoclastic bone resoφtion followed by osteoblastic bone formation. Although recent evidence suggests that GH participates in bone remodelling, the exact mechanism remains unclear. The present series of in vitro studies aimed to clarify how GH affects bone formation and resorption. GH binding sites were found to be present in osteoblastic MC3T3-E1 cells. Bovine GH (bGH) increased DNA synthesis, stimulated alkaline phosphatase activity and enhanced both type I procollagen mRNA expression and collagen synthesis. GH also increased the expression of both IGF-I and IGF-binding protein-5 mRNA as well as the release of IGF-I from these cells. The addition of IGF-I or recombinant IGFBP-5 alone significantly increased ALP activity and type I procollagen mRNA expression. These findings indicate that GH acts directly on osteoblasts to stimulate bone formation and that IGF-I and IGFBP-5 are involved in GH-stimulated bone formation. GH also stimulated pit formation on dentine slices and osteoclast differentiation in stromal cell-containing mouse bone cell cultures, whereas it did not affect the bone-resorbing activity of isolated rabbit osteoclasts. The addition of IGF-I or rIGFBP-5 alone exhibited similar effects. These stimulatory effects of GH on pit formation and osteoclast differentiation were significantly blocked in the presence of neutralizing anti-IGF-I antibody. PCR products corresponding in size to the mouse GH receptor were detected in osteoclast precursor cells. GH stimulated osteoclast-like cell formation from these cells in the absence of stromal cells, and these osteoclast-like cells formed pits on dentine slices in the presence of MC3T3-G2/PA-6 stromal cells. These findings indicate that GH stimulates osteoclastic bone resoφtion through both its direct and indirect action on the maturation of osteoclast precursor cells and through its indirect activation of mature osteoclasts, possibly via stromal cells. In conclusion, GH stimulates osteoclastic bone resorption as well as osteoblastic bone formation in vitro, and locally produced IGF-I and/or IGFBP-5 are involved in the stimulation of bone remodelling by GH.

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“…Our recent study revealed that an age-related decline in GH secretion was involved in age-dependent bone loss and changes in body composition in elderly women (14). The present study focusing on perimenopausal women indicates that GH itself plays a crucial role in the physiological regulation and maintenance of bone mass and body composition.…”

Section: Biochemical Measurementsmentioning

confidence: 49%

Significance of GH-IGF-I Axis in Changes in Body Composition, Bone and Lipid Metabolism in Perimenopausal Women

Chihara

Sugimoto

1997

Clin Pediatr Endocrinol

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Body composition as well as bone and lipid metabolism change during human aging irrespective of gender. In females, however, menopause is a critical event during aging which noticeably affects bone and lipid metabolism. The abrupt decrease in estrogen levels at menopause is supposed to reduce the tone of the GH-IGF-I axis although there is insufficient evidence to support this as yet. We investigated the association between the menopause and changes in the GH-IGF-I axis and body composition and tried to clarify the relationship between these parameters in perimenopausal women. The bone mineral density (BMD) of the lumbar spine and mid-radius of 77 healthy Japanese women aged 45-55 years (31 premenopausal[PRE] and 46 postmenopausal [POST]) was measured by dual energy X-ray absorptiometry (DEXA) and single photon absorptiometry, respectively. Body composition (bone mineral content [BMC], lean body mass [LBM] and fat mass) was also measured by DEXA and the percentage of BMC, LBM, and fat was calculated by dividing each body composition value by the total body mass. Percentage trunk fat was calculated by dividing the trunk fat by the total fat mass. The nocturnal urinary GH concentration normalized by the creatinine concentration was used as an index of endogenous GH secretion. Urinary GH and plasma IGF-I levels were significantly lower in the POST than in the PRE group, but plasma IGFBP-2 and -3 levels did not differ. The BMD of the lumber spine and mid-radius was significantly lower in the POST group and correlated positively with IGF-I but not IGFBP-2 or -3 levels; metabolic markers of bone formation and resorption were also significantly increased. %BMC and %trunk fat were significantly higher and lower, respectively, in the POST group than in the PRE group; serum total cholesterol and triglyceride level were also high in this group. Urinary GH levels correlated positively with % LBM and negatively with %fat, %trunk fat, and serum total cholesterol and triglyceride levels; multiple regression analysis showed that this correlation was significant even when serum estradiol levels and age were taken into account. These parameters did not correlate with plasma IGF levels. These results indicate that menopause reduces the tone of the GH-IGF-I axis, which is probably responsible for decreased bone mass. Menopause also causes rapid changes in body composition and lipid metabolism, and these changes seem to correlate with the GH but not the IGF-I concentration.

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Effect of natural menopause on serum levels of IGF-I and IGF-binding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women

Cited by 57 publications

References 36 publications

The association of breast mitogens with mammographic densities

The association of breast mitogens with mammographic densities

The Action of GH/IGF-I/IGFBP in Osteoblasts and Osteoclasts

Significance of GH-IGF-I Axis in Changes in Body Composition, Bone and Lipid Metabolism in Perimenopausal Women

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