Anatomy and Physiology of the Hypothalamic-Pituitary-Gonadal (HPG) Axis

  • Andrew A. DwyerEmail author
  • Richard Quinton


The hypothalamic-pituitary-gonadal (HPG) axis is central for human reproduction. This axis includes neuroendocrine networks that integrate wide ranging internal and external inputs to coordinate reproductive competence. Gonadotrophin-releasing hormone (GnRH) is the principal regulator of reproduction. GnRH controls gonadotrophin secretion and subsequently, gonadal (testicular) function. The HPG axis is activated during foetal life, neonatally and in puberty through adulthood. This developmental perspective is important as these periods contribute to the proper formation and development of sexual structures in utero as well as the development and function of the system enabling reproductive capacity in adulthood. The HPG axis remains silenced during childhood and neuroendocrine re-activation triggers pubertal onset. In early puberty, nocturnal sleep-entrained GnRH-induced gonadotrophin secretion stimulates testicular development and the initial rise in sex steroids resulting in the appearance of secondary sexual characteristics. Progressively, this pulsatile neuroendocrine activity extends through the day and is regulated by negative feedback. Puberty culminates in sexual maturation and the reproductive capacity of adult life. Sperm development occurs in the seminiferous tubules of the testes and requires testosterone and other testicular products for normal spermatogenesis. Effective HPG axis function is needed for normal sexual function and fertility and contributes to overall health and well-being. This chapter is a mini-review for endocrine nurses providing a summary of HPG axis development, function and regulation. This targeted summary is intended to serve as a basis for understanding key elements relating to male reproductive endocrine disorders such as hypogonadism, sexual dysfunction and infertility.


Hypothalamus Pituitary Gonadotrophins Testes Spermatogenesis Testosterone Sexual function 



Anti-Müllerian hormone


Congenital hypogonadotrophic hypogonadism




Dehydroepieandrostenedione sulphate




Disorder of sex development


Erectile dysfunction


Follicle stimulating hormone


Gonadotrophin-releasing hormone


Human chorionic gonadotrophin


Hypogonadotrophic hypogonadism




Inhibin B


Insulin-like peptide 3


Kallmann syndrome


Luteinizing hormone


Phosphodiesterase type 5


Sertoli cell


Standard deviation


Sex hormone binding globulin


Seminiferous tubule


  1. Abreu AP, Kaiser UB. Pubertal development and regulation. Lancet Diabetes Endocrinol. 2016;4(3):254–64.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Ahmed SF, Achermann JC, Arlt W, Balen A, Conway G, Edwards Z, et al. Society for Endocrinology UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development (Revised 2015). Clin Endocrinol. 2016;84(5):771–88.CrossRefGoogle Scholar
  3. Balasubramanian R, Dwyer A, Seminara SB, Pitteloud N, Kaiser UB, Crowley WF Jr. Human GnRH deficiency: a unique disease model to unravel the ontogeny of GnRH neurons. Neuroendocrinology. 2010;92(2):81–99.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Bancalari RE, Gregory LC, McCabe MJ, Dattani MT. Pituitary gland development: an update. Endocr Dev. 2012;23:1–15.PubMedCrossRefGoogle Scholar
  5. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536–59.CrossRefGoogle Scholar
  6. Boehm U, Bouloux PM, Dattani MT, de Roux N, Dode C, Dunkel L, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism-pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015;11(9):547–64.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Boepple PA, Hayes FJ, Dwyer AA, Raivio T, Lee H, Crowley WF Jr, 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(5):1809–14.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Boyar RM, Rosenfeld RS, Kapen S, Finkelstein JW, Roffwarg HP, Weitzman ED, et al. Human puberty. Simultaneous augmented secretion of luteinizing hormone and testosterone during sleep. J Clin Invest. 1974;54(3):609–18.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Buvat J, Maggi M, Gooren L, Guay AT, Kaufman J, Morgentaler A, et al. Endocrine aspects of male sexual dysfunctions. J Sex Med. 2010;7(4 Pt 2):1627–56.PubMedCrossRefGoogle Scholar
  10. Corona G, Rastrelli G, Maseroli E, Forti G, Maggi M. Sexual function of the ageing male. Best Pract Res Clin Endocrinol Metab. 2013;27(4):581–601.PubMedCrossRefGoogle Scholar
  11. Corona G, Isidori AM, Buvat J, Aversa A, Rastrelli G, Hackett G, et al. Testosterone supplementation and sexual function: a meta-analysis study. J Sex Med. 2014;11(6):1577–92.PubMedCrossRefGoogle Scholar
  12. Corona G, Isidori AM, Aversa A, Burnett AL, Maggi M. Endocrinologic control of men’s sexual desire and arousal/erection. J Sex Med. 2016;13(3):317–37.PubMedCrossRefGoogle Scholar
  13. Dean JD, McMahon CG, Guay AT, Morgentaler A, Althof SE, Becher EF, et al. The International Society for Sexual Medicine’s Process of Care for the Assessment and Management of Testosterone Deficiency in Adult Men. J Sex Med. 2015;12(8):1660–86.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Dwyer AA, Jayasena CN, Quinton R. Congenital hypogonadotropic hypogonadism: implications of absent mini-puberty. Minerva Endocrinol. 2016;41(2):188–95.Google Scholar
  15. Finkelstein JS, Lee H, Leder BZ, Burnett-Bowie SA, Goldstein DW, Hahn CW, et al. Gonadal steroid-dependent effects on bone turnover and bone mineral density in men. J Clin Invest. 2016;126(3):1114–25.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Georgiadis JR, Kringelbach ML, Pfaus JG. Sex for fun: a synthesis of human and animal neurobiology. Nat Rev Urol. 2012;9(9):486–98.PubMedCrossRefGoogle Scholar
  17. Groth KA, Skakkebaek A, Host C, Gravholt CH, Bojesen A. Clinical review: Klinefelter syndrome--a clinical update. J Clin Endocrinol Metab. 2013;98(1):20–30.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Grumbach MM. A window of opportunity: the diagnosis of gonadotropin deficiency in the male infant. J Clin Endocrinol Metab. 2005;90(5):3122–7.PubMedCrossRefGoogle Scholar
  19. Hatipoglu N, Kurtoglu S. Micropenis: etiology, diagnosis and treatment approaches. J Clin Res Pediatr Endocrinol. 2013;5(4):217–23.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Joustra SD, van der Plas EM, Goede J, Oostdijk W, Delemarre-van de Waal HA, Hack WW, et al. New reference charts for testicular volume in Dutch children and adolescents allow the calculation of standard deviation scores. Acta Paediatr. 2015;104(6):e271–8.PubMedCrossRefGoogle Scholar
  21. Kuiri-Hanninen T, Sankilampi U, Dunkel L. Activation of the hypothalamic-pituitary-gonadal axis in infancy: minipuberty. Horm Res Paediatr. 2014;82(2):73–80.PubMedCrossRefGoogle Scholar
  22. Nargund VH. Effects of psychological stress on male fertility. Nat Rev Urol. 2015;12(7):373–82.PubMedCrossRefGoogle Scholar
  23. Neto FT, Bach PV, Najari BB, Li PS, Goldstein M. Spermatogenesis in humans and its affecting factors. Semin Cell Dev Biol. 2016;59:10–26.PubMedCrossRefGoogle Scholar
  24. Pitteloud N, Dwyer AA, DeCruz S, Lee H, Boepple PA, Crowley WF Jr, 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(3):784–91.PubMedCrossRefGoogle Scholar
  25. Raivio T, Avbelj M, McCabe MJ, Romero CJ, Dwyer AA, Tommiska J, et al. Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. J Clin Endocrinol Metab. 2012;97(4):E694–9.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Rey RA, Grinspon RP, Gottlieb S, Pasqualini T, Knoblovits P, Aszpis S, et al. Male hypogonadism: an extended classification based on a developmental, endocrine physiology-based approach. Andrology. 2013;1(1):3–16.PubMedCrossRefGoogle Scholar
  27. Ritzen EM, Bergh A, Bjerknes R, Christiansen P, Cortes D, Haugen SE, et al. Nordic consensus on treatment of undescended testes. Acta Paediatr. 2007;96(5):638–43.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH pathway in human reproductive health and disease. Hum Reprod Update. 2014;20(4):485–500.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Sykiotis GP, Hoang XH, Avbelj M, Hayes FJ, Thambundit A, Dwyer A, et al. Congenital idiopathic hypogonadotropic hypogonadism: evidence of defects in the hypothalamus, pituitary, and testes. J Clin Endocrinol Metab. 2010;95(6):3019–27.PubMedPubMedCentralCrossRefGoogle Scholar
  30. Yafi FA, Jenkins L, Albersen M, Corona G, Isidori AM, Goldfarb S, et al. Erectile dysfunction. Nat Rev Dis Primers. 2016;2:16003.PubMedPubMedCentralCrossRefGoogle Scholar

Key Reading

  1. 1.
    Abreu AP, Kaiser UB. Pubertal development and regulation. Lancet Diabetes Endocrinol. 2016;4(3):254–64. Scholar
  2. 2.
    Boehm U, Bouloux PM, Dattani MT, de Roux N, Dodé C, Dunkel L, Dwyer AA, Giacobini P, Hardelin J-P, Juul A, Maghnie M, Pitteloud N, Prevot V, Raivio T, Tena-Sempere M, Quinton R, document YJE c. European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment. Nat Rev. Endocrinol. 2015;11(9):547–64. Scholar
  3. 3.
    Rey RA, Grinspon RP, Gottlieb S, Pasqualini T, Knoblovits P, Aszpis S, Pacenza N, Stewart Usher J, Bergadá I, Campo SM. Male hypogonadism: an extended classification based on a developmental, endocrine physiology-based approach. Andrology. 2013;1(1):3–16. Scholar
  4. 4.
    Neto FT, Bach PV, Najari BB, Li PS, Goldstein M. Spermatogenesis in humans and its affecting factors. Semin Cell Dev Biol. 2016. pii: S1084–9521(16)30104–5. Scholar
  5. 5.
    Yafi FA, Jenkins L, Albersen M, Corona G, Isidori AM, Goldfarb S, Maggi M, Nelson CJ, Parish S, Salonia A, Tan R, Mulhall JP, Hellstrom WJ. Erectile dysfunction. Nat Rev Dis Primers. 2016;2:16003. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.William F. Connell School of NursingChesnut HillUSA
  2. 2.Boston CollegeChesnut HillUSA
  3. 3.Newcastle-upon-Tyne Hospitals Foundation NHS Trust (Royal Victoria Infirmary), Institute for Human Genetics, University of Newcastle-upon-TyneNewcastle-upon-TyneUK

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