BADERC-Anne Klibanski

Anne Klibanski, M.D.

Growth Hormone and IGF-1 Actions on Bone Metabolism and Cardiovascular Risk

A major research focus in the Neuroendocrine Unit is the role of growth hormone (GH) and IGF-1 on bone metabolism. We have identified severe osteopenia in patients with GH deficiency as well as in patients with acquired GH resistance and IGF-1 deficiency due to undernutrition. The effects of GH action on osteoblast function in such groups is under investigation as is the use of rhIGF-1 to reverse these effects. Short-term studies have identified a specific stimulatory effect on osteoblast function during rhIGF-1 administration. Studies are underway to determine the chronic effects of rhIGF-l administration on bone mass and its relationship to gonadal steroids. A second area focuses on the investigation of the effects of GH deficiency and rhGH administration on cardiovascular risk, specifically effects on inflammatory markers. CRP levels are markedly elevated in patients with acquired GH deficiency and we have shown that they improve markedly following physiologic GH administration. Growth hormone deficiency is associated with abnormalities in insulin action and effects of GH administration on these parameters is also under investigation

References:

Misra M, Miller KK, Griffin K, Stewart V, Hunter E, Herzog DB, Klibanski A. Secretory dynamics of leptin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiology Endocrinol Metab. 2005; 289:373-81.
Misra M, Miller KK, Kuo K, Griffin K, Stewart V, Hunter E, Herzog DB, Klibanski A. Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiology Endocrinol Metab. 2005; 289:347-56.
Misra M, Miller KK, Stewart V, Hunter E, Kuo K, Herzog DB, Klibanski A. Ghrelin and bone metabolism in adolescent girls with anorexia nervosa and healthy adolescents. J Clin Endocrinol Metab. 2005; 90(9):5082-7.
Miller KK, Lee EE, Lawson E, Misra M, Minihan J, Grinspoon SK, Gleysteen S, Mickley D, Herzog D, Klibanski A. Determinants of skeletal recovery in anorexia nervosa. J Clin Endocrinol Metab. 2006; 91:2931-7.
Miller KK, Lawson E, Mathur V, Wexler T, Meenaghan E, Herzog D, Klibanski A. Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. J Clin Endocrinol Metab. 2007; 92(4):1334-9.
Miller KK, Biller BMK, Schaub A, Pulaski-Liebert K, Bradwin G, Rifai N, Klibanski A. Effects of testosterone therapy on cardiovascular risk markers in androgen-deficient women with hypopituitarism. J Clin Endocrinol Metab. 2007; 92(7):2474-9.
Misra M, Miller KK, Cord J, Prabhakaran R, Goldstein M, Katzman DK, Herzog DB, Klibanski A. Relationship between serum adipokines, insulin levels and bone density in adolescent girls with anorexia nervosa and controls. J Clin Endocrinol Metab. 2007; 92:2046-52.
Ansell PJ, Zhou Y, Schjeide BM, Kerner A, Zhao J, Zhang X, Klibanski A. Regulation of growth hormone expression by delta-like protein 1 (Dlk1). Mol Cell Endocrinol. 2007; 271:55-63.
Misra M, Prabhakaran R, Miller KK, Goldstein MA, Mickley D, Clauss L, Lockhart P, Cord J, Herzog DB, Katzman DK, Klibanski A. Prognostic indicators of changes in bone density measures in adolescent girls with anorexia nervosa-II. J Clin Endocrinol Metab. 2008; 93(4):1292-7.
Beauregard C*, Utz A*, Schaub AE, Nachtigall L, Biller BMK, Miller KK, Klibanski A. Growth hormone (GH) decreases visceral fat and improves cardiovascular risk (CV) markers in women with hypopituitarism: a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2008; 93(6):2063-71.






			Anne Klibanski, M.D. Growth Hormone and IGF-1 Actions on Bone Metabolism and Cardiovascular Risk A major research focus in the Neuroendocrine Unit is the role of growth hormone (GH) and IGF-1 on bone metabolism. We have identified severe osteopenia in patients with GH deficiency as well as in patients with acquired GH resistance and IGF-1 deficiency due to undernutrition. The effects of GH action on osteoblast function in such groups is under investigation as is the use of rhIGF-1 to reverse these effects. Short-term studies have identified a specific stimulatory effect on osteoblast function during rhIGF-1 administration. Studies are underway to determine the chronic effects of rhIGF-l administration on bone mass and its relationship to gonadal steroids. A second area focuses on the investigation of the effects of GH deficiency and rhGH administration on cardiovascular risk, specifically effects on inflammatory markers. CRP levels are markedly elevated in patients with acquired GH deficiency and we have shown that they improve markedly following physiologic GH administration. Growth hormone deficiency is associated with abnormalities in insulin action and effects of GH administration on these parameters is also under investigation References: Misra M, Miller KK, Griffin K, Stewart V, Hunter E, Herzog DB, Klibanski A. Secretory dynamics of leptin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiology Endocrinol Metab. 2005; 289:373-81. Misra M, Miller KK, Kuo K, Griffin K, Stewart V, Hunter E, Herzog DB, Klibanski A. Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents. Am J Physiology Endocrinol Metab. 2005; 289:347-56. Misra M, Miller KK, Stewart V, Hunter E, Kuo K, Herzog DB, Klibanski A. Ghrelin and bone metabolism in adolescent girls with anorexia nervosa and healthy adolescents. J Clin Endocrinol Metab. 2005; 90(9):5082-7. Miller KK, Lee EE, Lawson E, Misra M, Minihan J, Grinspoon SK, Gleysteen S, Mickley D, Herzog D, Klibanski A. Determinants of skeletal recovery in anorexia nervosa. J Clin Endocrinol Metab. 2006; 91:2931-7. Miller KK, Lawson E, Mathur V, Wexler T, Meenaghan E, Herzog D, Klibanski A. Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. J Clin Endocrinol Metab. 2007; 92(4):1334-9. Miller KK, Biller BMK, Schaub A, Pulaski-Liebert K, Bradwin G, Rifai N, Klibanski A. Effects of testosterone therapy on cardiovascular risk markers in androgen-deficient women with hypopituitarism. J Clin Endocrinol Metab. 2007; 92(7):2474-9. Misra M, Miller KK, Cord J, Prabhakaran R, Goldstein M, Katzman DK, Herzog DB, Klibanski A. Relationship between serum adipokines, insulin levels and bone density in adolescent girls with anorexia nervosa and controls. J Clin Endocrinol Metab. 2007; 92:2046-52. Ansell PJ, Zhou Y, Schjeide BM, Kerner A, Zhao J, Zhang X, Klibanski A. Regulation of growth hormone expression by delta-like protein 1 (Dlk1). Mol Cell Endocrinol. 2007; 271:55-63. Misra M, Prabhakaran R, Miller KK, Goldstein MA, Mickley D, Clauss L, Lockhart P, Cord J, Herzog DB, Katzman DK, Klibanski A. Prognostic indicators of changes in bone density measures in adolescent girls with anorexia nervosa-II. J Clin Endocrinol Metab. 2008; 93(4):1292-7. Beauregard C, Utz A, Schaub AE, Nachtigall L, Biller BMK, Miller KK, Klibanski A. Growth hormone (GH) decreases visceral fat and improves cardiovascular risk (CV) markers in women with hypopituitarism: a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2008; 93(6):2063-71. .