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      Is breast cancer a potential side effect of GH treatment?

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      Nature Medicine
      Springer Nature

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          Effects of recombinant insulin-like growth factor-I and growth hormone on bone turnover in elderly women.

          We evaluated the effects of recombinant insulin-like growth factor-I (IGF-I) and growth hormone (GH) on calciotropic hormones and bone turnover markers in 16 healthy elderly women 71.9 +/- 1.3 years of age (mean +/- SEM). Subjects consumed a fixed diet providing 1000 mg of calcium and 0.9 g/kg of protein for 10 days before starting baseline 24-h urine and blood collections. Specimens were collected for 6 consecutive days before initiating subcutaneous injections of GH (25 micrograms/kg/day, n = 5) and IGF-I at 60 micrograms/kg b.i.d. (high-dose, n = 5) or at 15 micrograms/kg b.i.d. (low-dose, n = 6) for 28 days. Resorption markers included urine hydroxyproline (OHP), total pyridinolines (PYD), and N-telopeptide; formation markers include osteocalcin, skeletal alkaline phosphatase (sALP), and type I procollagen carboxy-terminal extension peptide (CICP). For each subject, baseline daily turnover markers varied substantially (DV = 16-22%). With GH and high-dose IGF-I, resorption and formation markers increased progressively to maximum levels at day 21. For GH, the increase in day 21 PYD, N-telopeptide, osteocalcin, and CICP was 143, 111, 53, and 81%, respectively (p < 0.96-0.02). For high-dose IGF-I, these increases were 108, 81, 77, and 111% (p < 0.02-0.002). However, with low-dose IGF-I no change was observed in resorption markers while osteocalcin and CICP increased progressively (day 21, % increases = 88 +/- 51, 36 +/- 14). Twenty-four hour urine collections during the last days of baseline and of study drug were taken as six 4 h aliquots. When deoxyPYD was measured on these samples in the low-dose IGF-I group, a significant increase was observed only on the 0800-1200 h aliquot. Serum phosphorus concentrations increased with GH (21.2 +/- 3.3%) and high-dose IGF-I (8.8 +/- 3.6%) by day 21 but actually decreased by day 28 (-9.7 +/- 2.7, p < 0.02) with low-dose IGF-I. Urinary phosphorus excretion decreased with high-dose IGF-I only. Twenty-four hour calcium excretion increased with all treatments. These results indicate that both GH and high-dose IGF-I activate remodeling osteons. By contrast, low-dose IGF-I may directly increase osteoblastic function with only a minimal increase in bone resorption and may therefore provide a useful means to increase bone mass. The results also suggest some of the GH action on renal phosphorus handling represents a direct action of GH on the nephron which does not involve the intermediacy of IGF-I. Finally, even under controlled conditions bone turnover markers exhibit substantial daily variation so that a very large treatment effect will be required for these markers to have clinical utility.
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            Growth hormone treatment induces mammary gland hyperplasia in aging primates.

            The decline of growth hormone (GH) and insulin-like growth factor I (IGF-I) production during aging has been likened to the decrease in gonadal steroids in menopause. The repletion of GH/IGF-I levels in aging individuals is suggested to restore the lean tissue anabolism characteristic of youth. In addition to anabolic effects on musculo-skeletal tissues, GH also stimulates mammary glandular growth in some species, although its effects on primate mammary growth remain unclear. Some clinical observations implicate GH in human mammary growth, for example, gynecomastia occurs in some children treated with GH (ref. 6), and tall stature and acromegaly are associated with an increased incidence of breast cancer. To investigate the effects of GH/IGF-I augmentation on mammary tissue in a model relevant to aging humans, we treated aged female rhesus monkeys with GH, IGF-I, GH + IGF-I or saline diluent for 7 weeks. IGF-I treatment was associated with a twofold increase, GH with a three- to fourfold increase, and GH + IGF-I with a four'-to fivefold increase in mammary glandular size and epithelial proliferation index. These mitogenic effects were directly correlated with circulating GH and IGF-I levels, suggesting that either GH or its downstream effector IGF-I stimulates primate mammary epithelial proliferation.
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              New insights in the molecular mechanism of progestin-induced proliferation of mammary epithelium: Induction of the local biosynthesis of growth hormone (GH) in the mammary gland of dogs, cats and humans

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                Author and article information

                Journal
                Nature Medicine
                Nat Med
                Springer Nature
                1078-8956
                1546-170X
                October 1997
                October 1 1997
                October 1997
                : 3
                : 10
                : 1081-1082
                Article
                10.1038/nm1097-1081
                a0d3832e-04a6-47c5-83f2-7387e5f62e0e
                © 1997

                http://www.springer.com/tdm

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