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Chapter 11 Companion site for Basic Medical Endocrinology, 4th Edition Author: Dr. Goodman.

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Presentation on theme: "Chapter 11 Companion site for Basic Medical Endocrinology, 4th Edition Author: Dr. Goodman."— Presentation transcript:

1 Chapter 11 Companion site for Basic Medical Endocrinology, 4th Edition Author: Dr. Goodman

2 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 2 Hormonal regulation of growth at different stages of life. IGFs = insulin-like growth factors; GH = growth hormone; T3 = triiodothyronine. FIGURE 11.1

3 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 3 A. Typical growth curves for boys and girls. Note that growth is not linear and that it proceeds at the same rate in juvenile boys and girls. At puberty, which begins earlier in girls than in boys, there is a spurt in growth that immediately precedes growth arrest. B. Nonlinearity of growth is more clearly evident when plotted as changes in growth velocity over time. Note that growth, which is very rapid in the newborn, slows during the juvenile period and accelerates at puberty. FIGURE 11.2

4 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 4 Schematic representation of the tibial epiphyseal growth plate. (Modified from Nilsson, O., Marino, R., De Luca, F., Phillip, M., and Baron, J. (2005) Endocrine regulation of the growth plate. Hormone Research 64: 157–165.) FIGURE 11.3

5 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 5 Insulin-like growth factor-I (IGF-I) treatment of children with growth hormone (GH) insensitivity due to a receptor deficiency compared to GH treatment of children with GH deficiency. (Plotted from data of Guevara-Aguirre, J., Rosenbloom, A.L., Vasconez, O., Martinez, V, Gargosky, S., Allen, L., Rosenfeld, R. (1997) Two-year treatment of growth hormone (GH) receptor deficiency with recombinant insulin-like growth factor-I in 22 children: Comparison of two dosage levels to GH- treated deficiency. J. Clin. Endocrinol. Metab. 82: 629–633.) FIGURE 11.4

6 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 6 The roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in promoting growth. GH stimulates IGF-I production in liver and epiphyseal growth plates. Epiphyseal growth is stimulated primarily by autocrine/paracrine actions of IGF-I. IGF-I produced by the liver accounts for growth in diameter of bones and acts as a negative feedback regulator of GH secretion. Liver is the principal source of IGF-I in blood, but other GH target organs may also contribute to the circulating pool. FIGURE 11.5

7 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 7 Proinsulin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-II (IGF-II). Structures are drawn to emphasize similarities. Amino acid sequences show about 50% identity in the regions corresponding to the A and B chains of all three compounds, and more than 74% identity in the IGFs. The C chain regions have the most variability. FIGURE 11.6

8 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 8 Effects of human growth hormone (hGH) on nitrogen, sodium, potassium, and phosphorus balances in an 11.5-year-old girl with pituitary dwarfism. Changes above the control baseline represent retention of the substance; changes below the line represent loss. (From Hutchings, J.J., Escamilla, R.F., Deamer, W.C. et al. (1959) Metabolic changes produced human growth hormone in a pituitary dwarf. J. Clin. Endocrinol. Metab. 19: 759–764.) FIGURE 11.7

9 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 9 Growth hormone concentrations in blood sampled at 10-minute intervals over a 24-hour period in a normal man (panel A) and a normal woman (panel B). The large pulse in A coincides with the early hours of sleep. Note that the pulses of secretion are more frequent and of greater amplitude in the woman. (From Asplin, C.M., Faria, H.C.S., Carlsen, E.C. et al. (1989) Alterations in the pulsatile mode of growth hormone release in men and women with insulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 69: 239–245.) FIGURE 11.8

10 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 10 Relation between the integrated plasma concentration of GH and age in 173 normal males and females. (From Zadik, Z., Chalew, S.A., McCarter, R.J. Jr, Meistas, M., Kowarski, A.A. (1985) The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals. J. Clin. Endocrinol. Metab. 60: 513–516.) FIGURE 11.9

11 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 11 Changing patterns of GH secretion with age. (Modified from Robinson, I.C.A.F., Hindmarsh, P.C. (1999) The growth hormone secretory pattern and statural growth. In Kostyo, J.L., Ed. Handbook of Physiology, Section 7, The Endocrine System, Vol. V Hormonal Control of Growth. Oxford University Press, New York, 329–396.) FIGURE 11.10

12 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 12 Acute changes in plasma growth hormone concentration (upper panel) in response to insulin- induced hypoglycemia (lower panel). (From Roth, J., Glick, S.M., Yalow, R.S., and Berson, S. (1963) Hypoglycemia: A potent stimulus to secretion of growth hormone. Science 140: 987–989.) FIGURE 11.11

13 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 13 Effects of insulin-like growth factor-I (IGF-I) on growth hormone (GH) secretion in normal fasted men. Values shown are averages for the same 10 men given infusions of either physiological saline (control) or IGF-I for the periods indicated. Note: IGF-I completely blocked GH secretion after a lag period of 1 hour. (Redrawn from Hartman, M.L., Clayton, P.E., Johnson, M.L., Celniker, A., Perlman, A.J., Alberti, K.G., and Thorner, M.O. (1993) A low dose euglycemic infusion of recombinant human insulin-like growth factor-I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans. J. Clin. Invest. 91: 2453–2462.) FIGURE 11.12

14 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 14 Regulation of growth hormone (GH) secretion. PVN = periventricular nuclei; ARC = arcuate nuclei; SST = somatostatin; GHRH = growth hormone releasing hormone; IGF-I = insulin-like growth factor-I; (+) = stimulation. ( ) = inhibition. FIGURE 11.13

15 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 15 Effects of growth hormone releasing hormone (GHRH), insulin-like growth factor-I (IGF-I), somatostatin (SST), and ghrelin on the somatotrope. GHRHR = GHRH receptor. cAMP = cyclic adenosine monophosphate; CREB = cAMP response element binding protein; PKA = protein kinase A; PIT-1 = pituitary-specific transcription factor-1; PPase = protein phosphatase; PLC = phospholipase C; IP3 = inositol trisphosphate. Green arrows indicate activation; red arrows indicate inhibition. Opposing effects of GHRH and SST on Na+ and K+ lead to depolarization and activation of voltage-sensitive Ca2+ channels (GHRH) or hyperpolarization (SST) and prevention of Ca2+ channel activation. See text for discussion. FIGURE 11.14

16 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 16 Nocturnal plasma concentrations of growth hormone in a hypothyroid boy in the early stages of puberty before and 2 months after treatment with thyroxine. Each bar represents the average plasma GH concentration during a 30-minute period of continuous slow withdrawal of blood. Plasma IGF-I was increased more than fourfold during treatment. (From Chernausek, S.D. and Turner, R. (1989) Attenuation of spontaneous nocturnal growth hormone secretion in children with hypothyroidism and its correlation with plasma insulin-like growth factor I concentrations. J. Pedatr. 114: 965–972.) FIGURE 11.15

17 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 17 Effects of thyroxine on the plasma concentrations of IGF-I and IGF-II (Panel A) and IGF binding protein-3 (Panel B) in 10 thyroidectomized subjects following cessation and resumption of thyroxine (T4) treatment. Note the long delay in responses to both hormone deprivation and recommenced treatment. (From Miell. J.P., Zini, M., Quin, J.D., Jones, J., Portioli, I., and Valcavi, R. (1994) Reversible effects of cessation and recommencement of thyroxine treatment on insulinlike growth factors (IGFs) and IGF-binding proteins in patients with total thyroidectomy. J. Clin. Endocrinol. Metab. 79: 1507–1512). FIGURE 11.16

18 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 18 Decreased growth hormone (GH) secretion in response to a test dose of growth hormone releasing hormone (GHRH) in hypothyroid, normal, and hyperthyroid individuals. Data shown represent average responses from 30 normal, 25 hypothyroid, and 38 hyperthyroid adult patients. (From Valcavi, R., Zini, M., Portioli, M. (1992) Thyroid hormones and growth hormone secretion. J. Endocrinol. Invest. 15: 313–330.) FIGURE 11.17

19 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 19 Requirement of insulin for normal growth in response to GH. Rats were pancreatectomized 3 to 7 weeks before the experiment was begun. Each rat was fed 7 g of food per day. The treated group was injected with the indicated amounts of GH daily. Note the failure to respond to GH in the period between 20 and 44 days, coincident with the decrease in daily insulin dose, and the resumption of growth when the daily dose of insulin was restored. (From Scow, R.O., Wagner, E.M., and Ronov, E. (1958) Effect of growth hormone and insulin on body weight and nitrogen retention in pancreatectomized rats. Endocrinology 62: 593–604.) FIGURE 11.18

20 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 20 Growth curves of men with inactivating mutations of the alpha estrogen receptor (red line) or P450 aromatase (green line). Compared to normal (blue line). Standard deviations above and below normal are shown. (From Smith, E.P., Boyd, J., Frank, G.R., Takahashi, H., Cohen, R.M., Specker, B., Williams, T.C., Lubahn, D.B., Korach, K.S. (1994) Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N. Engl. J. Med. 331: 1056–1061; and Morishima, A., Grumbach, M.M., Simpson, E.R., Fisher, C., Qin, K. (1995) Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J. Clin. Endocrinol. Metab. 80: 3689–3698.) FIGURE 11.19

21 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 21 Changes in plasma IGF-I and GH concentrations in the peripubertal period in normal boys. Bars in the lower panel indicate 24 hour integrated concentrations of GH. The blue curve is the idealized growth velocity curve for North American boys. (Upper panel from Juul, A., Dalgaard, P., Blum, W.F., Bang, P., Hall, K., Michaelsen, K.F., Muller, J., Skakkebaek, N.E. (1995) Serum levels of insulin-like growth factor (IGF)- binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: The relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. J. Clin. Endocrinol. Metab. 80: 2534–2542. Lower panel from Martha, P.M. Jr., Rogol, A.D., Veldhuis, J.D., Kerrigan. J.R., Goodman. D.W., Blizzard, R.M. (1989) Alterations in pulsatile properties of circulating growth hormone concentrations during puberty in boys. J. Clin. Endocr. Metab. 69: 563–570.) FIGURE 11.20

22 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 22 Effects of testosterone in a boy with short stature and delayed puberty. A. Before testosterone. B. During therapy with long-acting testosterone. Note the increase in frequency and amplitude of growth hormone secretory episodes in the treated subjects. (From Link, K., Blizzard, R.M., Evans, W. S., Kaiser, D.L., Parker, M.W., Rogol, A.D. (1986) The effect of androgens on the pulsatile release and the twenty-four-hour mean concentration of growth hormone in peripubertal males. J. Clin. Endocrinol. Metab. 62: 159–164.) FIGURE 11.21

23 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 23 Effects of cortisone on growth in hypophysectomized rats given GH replacement. The growth- promoting response to GH, measured as a change in either body weight or length, decreased progressively as the dose of cortisone was increased from 0.1 to 1.0 mg per day. The decrease in body weight seen when 1.0 mg per day of cortisone was given probably results from net breakdown of muscle mass (see Chapter 4). (From Soyka, L.F. and Crawford, J.D. (1965) Antagonism by cortisone of the linear growth induced in hypopituitary patients and hypophysectomized rats by human growth hormone. J. Clin. Endocrinol. Metab. 25: 469–475.) FIGURE 11.22

24 Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved. 24 Effects of hormones on the epiphyseal growth plate. FIGURE 11.23


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