Book contents
- Infertility in the Male
- Infertility in the Male
- Copyright page
- Contents
- Contributors
- Foreword
- Abbreviations
- Introduction
- Section 1 Scientific Foundations of Male Infertility
- Chapter 1 Anatomy and Embryology of the Male Reproductive Tract and Gonadal Development, the Epididymis, and Accessory Sex Organs
- Chapter 2 Cellular Architecture and Function of the Testis
- Chapter 3 Maturation and Function of Sperm
- Chapter 4 The Male Reproductive Endocrine System
- Chapter 5 Erection, Emission, and Ejaculation
- Chapter 6 Genomics, Epigenetics, and Male Reproduction
- Section 2 Clinical Evaluation of the Infertile Male
- Section 3 Laboratory Diagnosis of Male Infertility
- Section 4 Treatment of Male Infertility
- Section 5 Health Care Systems and Culture
- Index
- References
Chapter 4 - The Male Reproductive Endocrine System
from Section 1 - Scientific Foundations of Male Infertility
Published online by Cambridge University Press: 08 July 2023
Book contents
- Infertility in the Male
- Infertility in the Male
- Copyright page
- Contents
- Contributors
- Foreword
- Abbreviations
- Introduction
- Section 1 Scientific Foundations of Male Infertility
- Chapter 1 Anatomy and Embryology of the Male Reproductive Tract and Gonadal Development, the Epididymis, and Accessory Sex Organs
- Chapter 2 Cellular Architecture and Function of the Testis
- Chapter 3 Maturation and Function of Sperm
- Chapter 4 The Male Reproductive Endocrine System
- Chapter 5 Erection, Emission, and Ejaculation
- Chapter 6 Genomics, Epigenetics, and Male Reproduction
- Section 2 Clinical Evaluation of the Infertile Male
- Section 3 Laboratory Diagnosis of Male Infertility
- Section 4 Treatment of Male Infertility
- Section 5 Health Care Systems and Culture
- Index
- References
Summary
The male reproductive endocrine system function is strictly dependent on the dynamic interplay between neural and hormonal signals originating from the hypothalamus where specific neurons secrete gonadotropin-releasing hormone (GnRH) in an episodic pattern of pulses under the control of excitatory and inhibitory signals from neuromodulators, the anterior pituitary where GnRH binds to its own receptors on a specific pituitary cell type to stimulate pituitary gonadotropin secretion, and the testes where the trophic actions of gonadotropins result in the promotion of spermatogenesis and secretion of testicular steroids and peptides, which, in turn, modulate hypothalamic and pituitary function in both positive and negative feedback loops.
- Type
- Chapter
- Information
- Infertility in the Male , pp. 62 - 76Publisher: Cambridge University PressPrint publication year: 2023
References
Further Reading
Campo, S, Ambao, V, Creus, S, et al. Carbohydrate complexity and proportions of serum FSH isoforms in the male: lectin-based studies. Mol Cell Endocrinol 2007;260–2:197–204.Google Scholar
Das, N, Kumar, TR. Molecular regulation of follicle-stimulating hormone synthesis, secretion and action. J Mol Endocrinol 2018;60:R131–55.Google Scholar
Moore, AM, Coolen, LM, Porter, DT, Goodman, RL, Lehman, MN. KNDy cells revisited. Endocrinology 2018;159:3219–34.Google Scholar
References
Herbison, A. Physiology of the adult gonadotropin-releasing hormone neuronal network. In: Plant, TM, Zeleznik, AJ, eds. Knobil and Neill’s Physiology of Reproduction, 4th ed. Oxford: Academic Press, 2015; pp. 399–467.Google Scholar
Krsmanovic, LZ, Hu, L, Leung, PK, Feng, H, Catt, KJ. Pulsatile GnRH secretion: roles of G protein-coupled receptors, second messengers and ion channels. Mol Cell Endocrinol 2010;314:158–63.Google Scholar
Krsmanovic, LZ, Stojilkovic, SS, Mertz, LM, Tomic, M, Catt, KJ. Expression of gonadotropin-releasing hormone receptors and autocrine regulation of neuropeptide release in immortalized hypothalamic neurons. Proc Natl Acad Sci U S A 1993;90:3908–12.Google Scholar
Xu, C, Xu, XZ, Nunemaker, CS, Moenter, SM. Dose-dependent switch in response of gonadotropin-releasing hormone (GnRH) neurons to GnRH mediated through the type I GnRH receptor. Endocrinology 2004;145:728–35.Google Scholar
Cho, S, Han, J, Sun, W, et al. Evidence for autocrine inhibition of gonadotropin-releasing hormone (GnRH) gene transcription by GnRH in hypothalamic GT1-1 neuronal cells. Brain Res Mol Brain Res 1997;50:51–8.Google Scholar
Krsmanovic, LZ, Hu, L, Leung, PK, Feng, H, Catt, KJ. Pulsatile GnRH secretion: roles of G protein-coupled receptors, second messengers and ion channels. Mol Cell Endocrinol 2010;314:158–63.Google Scholar
Clarkson, J, Han, SY, Piet, R, et al. Definition of the hypothalamic GnRH pulse generator in mice. Proc Natl Acad Sci U S A 2017;114:E10216–23.Google Scholar
Seminara, SB, Messager, S, Chatzidaki, EE, et al. The GPR54 gene as a regulator of puberty. N Engl J Med 2003;349:1614–27.Google Scholar
Lanfranco, F, Gromoll, J, von Eckardstein, S, Herding, EM, Nieschlag, E, Simoni, M. Role of sequence variations of the GnRH receptor and G protein-coupled receptor 54 gene in male idiopathic hypogonadotropic hypogonadism. Eur J Endocrinol 2005;153:845–52.Google Scholar
Han, SK, Gottsch, ML, Lee, KJ, et al. Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci 2005;25:11349–56.Google Scholar
Topaloglu, AK, Reimann, F, Guclu, M, et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction. Nat Genet 2009;41:354–8.Google Scholar
Skorupskaite, K, George, JT, Anderson, RA. The kisspeptin–GnRH pathway in human reproductive health and disease. Hum Reprod Update 2014;20:485–500.Google Scholar
Moore, AM, Coolen, LM, Porter, DT, Goodman, RL, Lehman, MN. KNDy cells revisited. Endocrinology 2018;159:3219–34.Google Scholar
Pitteloud, N, Dwyer, AA, DeCruz, S, et al. Inhibition of luteinizing hormone secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem study of normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab 2008;93:784–91.Google Scholar
Hayes, FJ, Seminara, SB, DeCruz, S, Boepple, PA, Crowley, WF Jr. Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. J Clin Endocrinol Metab 2000;85:3027–35.Google Scholar
Smith, JT, Dungan, HM, Stoll, EA, et al. Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse. Endocrinology 2005;146:2976–84.Google Scholar
Mayer, CM, Fick, LJ, Gingerich, S, Belsham, DD. Hypothalamic cell lines to investigate neuroendocrine control mechanisms. Front Neuroendocrinol 2009;30:405–23.Google Scholar
Hu, L, Gustofson, RL, Feng, H, et al. Converse regulatory functions of estrogen receptor-alpha and -beta subtypes expressed in hypothalamic gonadotropin-releasing hormone neurons. Mol Endocrinol 2008;22:2250–9.Google Scholar
Kaprara, A, Huhtaniemi, IT. The hypothalamus–pituitary–gonad axis: tales of mice and men. Metabolism 2018;86:3–17.Google Scholar
Campo, S, Andreone, L, Ambao, V, et al. Hormonal regulation of follicle-stimulating hormone glycosylation in males. Front Endocrinol 2019;10:17.Google Scholar
Wide, L, Naessen, T, Sundstrom-Poromaa, I, Eriksson, K. Sulfonation and sialylation of gonadotropins in women during the menstrual cycle, after menopause, and with polycystic ovarian syndrome and in men. J Clin Endocrinol Metab 2007;92:4410–17.Google Scholar
Das, N, Kumar, TR. Molecular regulation of follicle-stimulating hormone synthesis, secretion and action. J Mol Endocrinol 2018;60:R131–55.Google Scholar
Manna, PR, Joshi, L, Reinhold, VN, et al. Synthesis, purification and structural and functional characterization of recombinant form of a common genetic variant of human luteinizing hormone. Hum Mol Genet 2002;11:301–15.Google Scholar
Sairam, MR, Fleshner, P. Inhibition of hormone-induced cyclic AMP production and steroidogenesis in interstitial cells by deglycosylated lutropin. Endocrinology 1981;22:41–54.Google Scholar
Simoni, M, Gromoll, J, Nieschlag, E. The follicle-stimulating hormone receptor: biochemistry; molecular biology, physiology, and pathophysiology. Endocr Rev 1997;18:739–73.Google Scholar
Tapanainen, JS, Aittomaki, K, Min, J, et al. Men homozygous for an inactivating mutation of the follicle-stimulating hormone (FSH) receptor gene present variable suppression of spermatogenesis and fertility. Nat Genet 1997;15:205–6.Google Scholar
Huhtaniemi, I, Alevizaki, M. Gonadotrophin resistance. Best Pract Res Clin Endocrinol Metab 2006;20:561–76.Google Scholar
Caroppo, E. Endocrine genetic defects. In: Skinner, MK, ed. Encyclopedia of Reproduction, 2nd ed, Vol. 4. Waltham, MA: Academic Press, 2018; pp. 252–7.Google Scholar
Thompson, IR, Kaiser, UB. GnRH pulse frequency-dependent differential regulation of LH and FSH gene expression. Mol Cell Endocrinol 2014;385:28–35.Google Scholar
Fortin, J, Lamba, P, Wang, Y, Bernard, DJ. Conservation of mechanisms mediating gonadotrophin-releasing hormone 1 stimulation of human luteinizing hormone beta subunit transcription. Mol Hum Reprod 2009;15:77–87.Google Scholar
Boepple, PA, Hayes, FJ, Dwyer, AA, et al. Relative roles of inhibin B and sex steroids in the negative feedback regulation of follicle-stimulating hormone in men across the full spectrum of seminiferous epithelium function. J Clin Endocrinol Metab 2008;93:1809–14.Google Scholar
Wijayarathna, R, de Kretser, DM. Activins in reproductive biology and beyond. Hum Reprod Update 2016;22:342–57.Google Scholar
Burger, LL, Haisenleder, DJ, Wotton, GM, Aylor, KW, Dalkin, AC, Marshall, JC. The regulation of FSHβ transcription by gonadal steroids: testosterone and estradiol modulation of the activin intracellular signaling pathway. Am J Physiol Endocrinol Metab 2007;293:E277–85.Google Scholar
Campo, S, Ambao, V, Creus, S, et al. Carbohydrate complexity and proportions of serum FSH isoforms in the male: lectin-based studies. Mol Cell Endocrinol 2007;260–2:197–204.Google Scholar
Bagatell, CJ, Dahl, KD, Bremner, WJ. The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol. J Androl 1994;15:15–21.Google Scholar
Schnorr, JA, Bray, MJ, Veldhuis, JD. Aromatization mediates testosterone’s short-term feedback restraint of 24-hour endogenously driven and acute exogenous gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone secretion in men. J Clin Endocrinol Metab 2001;86:2600–6.Google Scholar
Lindzey, J, Wetsel, WC, Couse, JF, Stoker, T, Cooper, R, Korach, KS. Effects of castration and chronic steroid treatments on hypothalamic gonadotropin-releasing hormone content and pituitary gonadotropins in male wild-type and estrogen receptor-α knockout mice. Endocrinology 1998;139:4092–101.Google Scholar
Veldhuis, JD, Takahashi, PY, Keenan, DM, Liu, PY, Mielke, KL, Weist, SM. Age disrupts androgen receptor-modulated negative feedback in the gonadal axis in healthy men. Am J Physiol Endocrinol Metab 2010;299:E675–82.Google Scholar
de Zegher, F, Devlieger, H, Veldhuis, JD. Pulsatile and sexually dimorphic secretion of luteinizing hormone in the human infant on the day of birth. Pediatr Res 1992;32:605–7.Google Scholar
Liu, PY, Beilin, J, Meier, C, et al. Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohorts. J Clin Endocrinol Metab 2007;92:3599–603.Google Scholar
Kaufman, JM, Vermeulen, A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005;26:833–76.Google Scholar
Roelfsema, F, Yang, RJ, Liu, PY, Takahashi, PY, Veldhuis, JD. Feedback on LH in testosterone-clamped men depends on the mode of testosterone administration and body composition. J Endocr Soc 2018;3:235–49.Google Scholar
Liu, PY, Pincus, SM, Takahashi, PY, et al. Aging attenuates both the regularity and joint synchrony of LH and testosterone secretion in normal men: analyses via a model of graded GnRH receptor blockade. Am J Physiol Endocrinol Metab 2006;290:E34–41.Google Scholar
Veldhuis, JD, Liu, PY, Takahashi, PY, Keenan, DM. Dynamic testosterone responses to near-physiological LH pulses are determined by the time pattern of prior intravenous LH infusion. Am J Physiol Endocrinol Metab 2012;303:E720–8.Google Scholar
Ascoli, M, Fanelli, F, Segaloff, DL. The lutropin/choriogonadotropin receptor, a 2002 perspective. Endocr Rev 2002;23:141–74.Google Scholar
Lin, T, Calkins, JK, Morris, PL, Vale, W, Bardin, CW. Regulation of Leydig cell function in primary culture by inhibin and activin. Endocrinology 1989;125:2134–40.Google Scholar
Chen, YC, Cochrum, RK, Tseng, MT, et al. Effects of CDB-4022 on Leydig cell function in adult male rats. Biol Reprod 2007;77:1017–26.Google Scholar
Xiao, F, Lan, A, Lin, Z, et al. Impact of CAG repeat length in the androgen receptor gene on male infertility – a meta-analysis. Reprod Biomed Online 2016;33:39–49.Google Scholar
Davey, RA, Grossman, M. Androgen receptor structure, function and biology: from bench to bedside. Clin Biochem Rev 2016;37:3–15.Google Scholar
Goldman, AL, Bhasin, S, Wu, FCW, Krishna, M, Matsumoto, AM, Jasuja, R. A reappraisal of testosterone’s binding in circulation: physiological and clinical implications. Endocr Rev 2017;38:302–24.Google Scholar
Hammes, A, Andreassen, TK, Spoelgen, R, et al. Role of endocytosis in cellular uptake of sex steroids. Cell 2005;122:751–62.Google Scholar
Keenan, DM, Takahashi, PY, Liu, PY, et al. An ensemble model of the male gonadal axis: illustrative application in aging men. Endocrinology 2006;147:2817–28.Google Scholar
Van Eenoo, P, Delbeke, FT. Metabolism and excretion of anabolic steroids in doping control – new steroids and new insights. J Steroid Biochem Mol Biol 2006;101:161–78.Google Scholar
Bulus, SE. Aromatase and estrogen receptor α deficiency. Fertil Steril 2014;101:323–9.Google Scholar
Anawalt, BD, Bebb, RA, Matsumoto, AM, et al. Serum inhibin B levels reflect Sertoli cell function in normal men and men with testicular dysfunction. J Clin Endocrinol Metab 1996;81:3341–5.Google Scholar
Marchetti, C, Hamdane, M, Mitchell, V, et al. Immunolocalization of inhibin and activin alpha and betaB subunits and expression of corresponding messenger RNAs in the human adult testis. Biol Reprod 2003;68:230–5.Google Scholar
Okuma, Y, O’Connor, AE, Hayashi, T, et al. Regulated production of activin A and inhibin B throughout the cycle of the seminiferous epithelium in the rat. J Endocrinol 2006;190:331–40.Google Scholar
Ivell, R, Heng, K, Anand-Ivell, R. Insulin-like factor 3 and the HPG axis in the male. Front Endocrinol (Lausanne) 2014;5:6.Google Scholar
Hutson, JM, Southwell, BR, Li, R, et al. The regulation of testicular descent and the effects of cryptorchidism. Endocr Rev 2013;34:725–52.Google Scholar
Bay, K, Virtanen, HE, Hartung, S, et al. Nordic Cryptorchidism Study Group, Toppari, J. Insulin-like factor 3 levels in cord blood and serum from children: effects of age, postnatal hypothalamic–pituitary–gonadal axis activation, and cryptorchidism. J Clin Endocrinol Metab 2007;92:4020–7.Google Scholar
Trabado, S, Maione, L, Bry-Gauillard, H, et al. Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients. J Clin Endocrinol Metab 2014;99:E268–75.Google Scholar
Kawamura, K, Kumagai, J, Sudo, S, et al. Paracrine regulation of mammalian oocyte maturation and male germ cell survival. Proc Natl Acad Sci U S A 2004;101:7323-8J.Google Scholar
Amory, JK, Page, ST, Anawalt, BD, Coviello, AD, Matsumoto, AM, Bremner, WJ. Elevated end-of-treatment serum INSL3 is associated with failure to completely suppress spermatogenesis in men receiving male hormone contraception. J Androl 2007;28:548–54.Google Scholar