Chapter 12 Companion site for Basic Medical Endocrinology, 4th Edition Author: Dr. Goodman

Chapter 12Companion site for Basic Medical Endocrinology, 4th Edition

Author: Dr. Goodman

Companion site for Basic Medical Endocrinology, 4th Edition. by Dr. Goodman Copyright © 2009 by Academic Press. All rights reserved.

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Histological section of human testis. The transected tubules show various stages of spermatogenesis. (From di Fiore, M.S.H. (1981) Atlas of Human Histology, 5th ed., 209. Lea & Febiger, Philadelphia.)

FIGURE 12.1


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Diagrammatic representation of the human testicular tubules. (From Netter, F.H. (1997) Atlas of Human Anatomy, 2nd edition, plate 362. Novartis, East Hanover.)

FIGURE 12.2


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The formation of mammalian germ cells. Each primary spermatogonium ultimately gives rise to 64 sperm cells. Cytokinesis is incomplete in all but the earliest spermatogonial divisions, resulting in expanding clones of germ cells that remain joined by intercellular bridges. Maturing spermatids are closely associated with and enfolded by the Sertoli cells.

FIGURE 12.3


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Ultrastructure of the Sertoli cell and its relation to the germ cells. The spermatocytes and early spermatids occupy niches in the sides of the columnar supporting cell, whereas late spermatids reside in deep recesses in its apex. (From Fawcett, D.W. (1986) A Textbook of Histology, 11th ed., 834. W.B. Saunders, Philadelphia.)

FIGURE 12.4


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Biosynthesis of testicular steroids. Catalyzed changes at each step are highlighted in colors. Testosterone comprises more than 99% of testicular steroid hormone production.

FIGURE 12.5


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Actions of FSH and LH on the testis. FSH acts directly only on Sertoli cells, whereas LH acts directly solely on Leydig cells. Paracrine cross-talk mediated by growth factors likely takes place between Sertoli and Leydig cells and between Sertoli cells and germ cells, and possibly between peritubular myoid cells and both Leydig and Sertoli cells. cAMP = cyclic adenosine monophosphate; PKA = protein kinase A; CREB = cyclic AMP response element binding protein; StAR = steroid acute regulatory protein; P450c17 = 17 hydroxylase/lyase; AR = androgen receptor; AMH = antimüllerian hormone; ABP = androgen binding protein.

FIGURE 12.6


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Metabolism of testosterone. Most of the testosterone secreted each day is degraded in the liver and other tissues by reduction of the A ring, oxidation of the 17 hydroxyl group, and conjugation with polar substituents. Conversion to 5- dihydrotestosterone takes place in target cells catalyzed mainly by the type II dehydrogenase and in nontarget cells mainly but not exclusively by the type I dehydrogenase. Aromatization of testosterone to estradiol may occur directly or after conversion to androstenedione. Note that 5- dihydrotestosterone cannot be aromatized or reconverted to testosterone.

FIGURE 12.7


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Action of testosterone. Testosterone (T) enters its target cell and binds to its nuclear androgen receptor (AR) either directly or after it is converted to 5-dihydrotestosterone (DHT). The thickness of the arrows reflects the quantitative importance of each reaction. The hormone–receptor complex binds to DNA along with a variety of cell-specific nuclear regulatory proteins to induce formation of the RNA that encodes the proteins that express effects of the hormone. Not shown: Testosterone may also bind to membrane receptors and initiate rapid ionic changes that may reinforce its genomic effects. Testosterone may also produce rapid changes in cyclic AMP production through the binding of the sex hormone binding globulin (SHBG) to surface receptors.

FIGURE 12.8


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Development of the testes and ovaries from common precursors in the genital ridges. SRY, (the sex-determining region of the Y chromosome), is the gene expressed only in cells that develop into Sertoli cells. In the absence of SRY these cells develop into follicle cells. Sertoli cells express SOX 9 and other transcription factors and the autocrine factor FGF9 (fibroblast growth factor 9) that lead to differentiation and multiplication of Sertoli cells. Enclosure of the primordial germ cells by Sertoli cells to form the primitive spermatic cords and unequivocal recognition of the primitive gonads as testes occurs as early as the seventh week. Subsequent recruitment of mesenchymal cells and their differentiation into Leydig cells takes place in response to the secreted factors DHH (desert hedgehog) and PDGF (platelet-derived growth factor). Newly differentiated Sertoli cells also secrete AMH (antimüllerian hormone) and inhibin. The first primordial follicles do not appear in the primitive ovary until the eleventh week.

FIGURE 12.9


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Development of the male and female internal genitalia. (From Jaffe, R. B. (1986) Disorders of sexual development. In Reproductive Endocrinology, 2nd ed., Yen, S.C. and Jaffe, R. B., eds., 283. W.B. Saunders, Philadelphia.)

FIGURE 12.10


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Normal development of the male and female reproductive tracts. Tissues destined to form the male tract are shown in blue; tissues that develop into the female tract are shown in pink. Bilateral castration of either male or female embryos results in development of the female pattern. Early unilateral castration of male embryos results in development of the normal male duct system on the side with the remaining gonad, but female development on the contralateral side. This pattern develops because both testosterone and antimüllerian hormone act as paracrine factors. (Modified from Jost. A. (1971) Embryonic sexual differentiation. In Hermaphroditism, Genital Anomalies and Related Endocrine Disorders, 2nd ed., Jones, H.W. and Scott, W.W., eds., 16, Williams & Wilkins, Baltimore.)

FIGURE 12.11


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Antimüllerian hormone (AMH) signaling pathway. AMH binds to its specific primary receptor (II), which then forms a heterodimer with and phosphorylates the secondary signal transducing subunit (I). The activated receptor complex then catalyzes phosphorylation of Smad proteins on serine and threonine residues causing them to bind Smad 4, which carries them into the nucleus where transcription of specific genes results in expression of an apoptotic program and resorption of the müllerian duct cells.

FIGURE 12.12


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Anomalies in male sexual development due to single gene mutations. A. Normal production of AMH (antimüllerian hormone), testosterone, and DHT (5- dihyrdrotestosterone) results in regression of the female internal organs and the development of internal and external male organs. B. Absence or defect in SRY (sexdetermining region of the Y chromosome) leads to ovarian agenesis and the otherwise normal development of female internal and external genitalia and the absence of any male characteristics. C. Absence of AMH leads to the development of both male and female internal genitalia and normal male external genitalia except that in some cases the presence of the female organs interferes with normal testicular descent into the scrotum. D. Absence of 17-hydroxylase or the androgen receptor results in an individual without an internal male or female reproductive tract, and with female external genitalia. E. Absence of 5-dehydrogenase II results in normal development of male internal organs, except the prostate, and normal regression of female internal sex organs. The external organs may be overtly female or ambiguous.

FIGURE 12.13


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LH secretory pattern observed in a normal 36 year old man. * = statistically significant discrete pulse. (From Crowley, W.F. Jr. (1985) In Current Topics in Endocrinology and Metabolism, Krieger, D.T. and Bardin, C.W., eds., 157. Marcel Decker, New York.)

FIGURE 12.14


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Recording of multiple unit activity (MUA) in the arcuate nuclei of conscious (A) and anesthetized (B) monkeys fitted with permanently implanted electrodes. Simultaneous measurements of LH in peripheral blood are shown in the upper tracings. (From Wilson, R.C., Kesner, J.S., Kaufman, J.N. et al. (1984) Central electrophysiologic correlates of pulsatile luteinizing hormone secretion in the rhesus monkey. Neuroendocrinology 39: 256.)

FIGURE 12.15


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The activins and inhibins are disulfide bonded dimers of the products of three separate genes. Inhibin B is the major circulating form in the human male, and is comprised of an alpha subunit and the beta B subunit. Activins are comprised of two beta subunits.

FIGURE 12.16


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Negative feedback regulation of testicular function. Green arrows = Stimulation. Red arrows = Inhibition. Blue arrows = crosstalk.

FIGURE 12.17


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Plasma LH and testosterone measured every 20 minutes reveal nocturnal pulsatile secretion of GnRH in a pubertal 14-year-old boy. (From Boyer, R.M., Rosenfeld, R.S., Kapen, S. et al. (1974) Simultaneous augmented secretion of luteinizing hormone and testosterone during sleep. J. Clin. Invest. 54: 609.)

FIGURE 12.18

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Chapter 12 Companion site for Basic Medical Endocrinology, 4th Edition Author: Dr. Goodman