Gonadotropins and the Hypothalamic Pituitary Axis - Podcast Version 0:00 / 0:00 1x 0.25x 0.5x 0.75x 1x 1.25x 1.5x 1.75x 2x The hypothalamic-pituitary-gonadal (HPG) axis is the hormonal system that controls reproduction, gamete production, and sex steroid synthesis. It involves the hypothalamus, pituitary gland, and gonads (testes and ovaries). The main hormones involved are: Gonadotropin-releasing hormone (GnRH), released from the hypothalamus Gonadotropins, including luteinising hormone (LH) and follicle-stimulating hormone (FSH) released by the anterior pituitary Sex steroids, including oestrogen, progesterone and testosterone, produced by the gonads This article will discuss the physiology of the HPG axis, its regulation, and its clinical relevance. 3D ModelPro Feature You've Discovered a Pro Feature Access our 3D Model Library Explore, cut, dissect, annotate and manipulate our 3D models to visualise anatomy in a dynamic, interactive way. Learn More Regulation of The HPG Axis Gonadotropin-Releasing Hormone (GnRH) is released in a pulsatile pattern from specialised neurons within the hypothalamus. GnRH neurons receive input from several areas of the brain, allowing reproductive function to be influenced by circadian rhythms, nutritional status, body fat, and stress. GnRH binds to its receptors on gonadotroph cells of the anterior pituitary, stimulating the secretion of luteinising hormone (LH) and follicle stimulating hormone (FSH). LH and FSH are also released in a pulsatile manner, reflecting the intermittent release of GnRH. LH and FSH travel in the bloodstream to the gonads (testes and ovaries), where they regulate gamete production and sex steroid synthesis. Artoria2e5, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons Fig 1Diagram showing the HPG axis and its regulation LH and FSH Function in Males In males, LH and FSH regulate testosterone production and spermatogenesis and support the function of other steroid hormones. Luteinising Hormone LH stimulates Leydig cells in the testes to produce testosterone, the principle male sex steroid hormone. Testosterone has several important physiological effects: Stimulates spermatogenesis (formation of sperm) in the testes Maintains libido (sexual drive) Promotes development of secondary sexual characteristics – including pubic, axillary and facial hair, deepening of the voice, increased muscle and bone mass Growth of male external genitalia Stimulates anabolic metabolism In some tissues, testosterone is converted to dihydrotestosterone (DHT), making up 10% of total circulating testosterone levels. DHT binds to the same androgen receptor as testosterone but with a higher affinity. Some tissues respond only to DHT, while others, such as the prostate, are more sensitive to DHT than testosterone. High levels of circulating testosterone suppress the HPG axis through negative feedback at the levels of the hypothalamus and the anterior pituitary, reducing further testosterone production. Created in BioRender Fig 2Diagram showing the effects of testosterone Follicle Stimulating Hormone FSH acts on Sertoli cells within the seminiferous tubules of the testes. It supports spermatogenesis (sperm production) and the synthesis of proteins required for the production and action of steroid hormones. Some proteins whose synthesis is promoted by FSH are listed in the table below: Protein Action Effect Androgen binding protein (ABP) Maintains high testosterone concentrations within seminiferous tubules (intratubular) Promote normal spermatogenesis P450 aromatase Converts testosterone into oestradiol Increases oestradiol Growth factors Promotes sperm cell survival, maturation and motility Support normal spermatogenesis Inhibin Selective inhibition of FSH (but not LH) secretion from anterior pituitary Inhibit activin (removing its suppression of Leydig cells) Regulate FSH secretion Indirectly promote testosterone secretion from Leydig cells LH and FSH Function in Females In females, LH and FSH regulate follicle development, ovulation, and the production and secretion of oestrogen and progesterone. Follicle Stimulating Hormone FSH acts on the granulosa cells of developing follicles to regulate follicular growth, oestrogen synthesis, and feedback within the HPG axis. It does this by exerting its effect on several proteins: Protein Action Effect Activins Positive feedback to anterior pituitary Enhance FSH secretion Steroidogenic enzymes (including aromatase) Increased steroid hormone synthesis Promote follicular growth Inhibin Selectively suppresses FSH secretion from the anterior pituitary Suppress further FSH secretion once a primary follicle has developed Contributes to the LH surge Aromatase Converts theca cell-derived androgens into oestrogen Promote oestrogen production Luteinising Hormone LH exerts its effects by acting on theca cells that surround developing ovarian follicles and granulosa cells at different stages of the ovarian cycle Overall Goal Action Effect Promote oestrogen production Stimulates theca cells to synthesise androgens Androgens diffuse into neighbouring granulosa cells, where FSH-induced aromatase converts them into oestrogen Increase granulosa cell responsiveness Oestrogen induces expression of LH receptors on granulosa cells Granulosa cells become increasingly responsive to LH as the follicle matures Promote completion of meiosis Stimulates granulosa cells Enables completion of meiosis before ovulation Trigger ovulation Increases ovarian collagenase activity Promotes follicular rupture and release of the oocyte Maintain the corpus luteum Acts on luteal cells following ovulation Supports corpus luteum function Promote steroidogenesis Stimulates the corpus luteum Increases progesterone and oestrogen secretion Created in BioRender Fig 3Diagram showing the effects of FSH (green) and LH (purple) in females Feedback Effects of Female Sex Steroid Hormones Oestrogen and progesterone regulate the HPG axis through positive and negative feedback at the hypothalamus and anterior pituitary. Progesterone is a sex steroid produced by the corpus luteum, which is the structure that forms from the ruptured follicle after ovulation. During most of the menstrual cycle, moderate oestrogen concentrations suppress LH and FSH secretion through negative feedback. In the late follicular phase, sustained high oestrogen levels (in the absence of progesterone) cause positive feedback, producing the LH surge that triggers ovulation. After ovulation, rising progesterone from the corpus luteum restores negative feedback, suppressing further LH and FSH secretion. Progesterone increases the inhibitory effect of moderate oestrogen concentration levels on LH and FSH secretion. It also prevents the positive feedback effect of high oestrogen concentrations on the pituitary. As a result, progesterone prevents further LH surges during the same menstrual cycle. If fertilisation has not taken place, levels of both progesterone and oestrogen fall. This removes the negative feedback on the hypothalamus, causing FSH to rise and subsequent oestrogen production These feedback effects are important to understanding the physiology of pharmacological contraception. Lopez, R. (2026). Ovarian Hormones Throughout the Menstrual Cycle. https://app.biorender.com/biorender-templates/details/t-642310511f9d75406597259a-ovarian-hormones-throughout-the-menstrual-cycle Fig 4Diagram showing the phases of the menstrual cycle and hormone changes throughout the cycle Phase Hormone levels Effect Feedback Mid-follicular Moderate oestrogen Suppresses LH and FSH Negative feedback Late-follicular High oestrogen and inhibin Increases LH (causing LH surge) but not FSH Positive feedback After ovulation Moderate oestrogen and progesterone Further suppresses LH and FSH Negative feedback Luteal High oestrogen and progesterone Prevents a rise in LH (prevents further LH surges) Negative feedback Menstruation/Early follicular Low oestrogen and progesterone Increases FSH Removes negative feedback Clinical Relevance Prostate Cancer Under normal physiological conditions, GnRH is released in a pulsatile pattern maintaining normal secretion of LH and FSH. Prolonged continuous exposure to GnRH causes its receptors on pituitary gonadotrophs to become internalised and degraded within lysosomes (receptor down-regulation). As receptor numbers decrease, the pituitary becomes less responsive to GnRH. Consequently, LH and FSH secretion falls, reducing stimulation of the testes. This process of GnRH receptor down-regulation can be induced for clinical benefit. In prostate cancer, long-acting GnRH agonists are administered to suppress LH and FSH secretion. This leads to a marked reduction in testosterone production and is known as medical (chemical) castration. Many prostate cancers are androgen-dependent, meaning that tumour growth is stimulated by testosterone. Therefore, medically lowering testosterone concentrations slows tumour growth and may reduce tumour size. Do you think you’re ready? Take the quiz below QuizPro Feature Gonadotropins and the Hypothalamic Pituitary Axis Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePhysiology Pro Challenge yourself with over 2100 multiple-choice questions to reinforce learning Learn More Frequent questions What are gonadotropins and their role in the reproductive system? Gonadotropins are hormones produced by the anterior pituitary gland, specifically luteinising hormone (LH) and follicle-stimulating hormone (FSH). They are essential for regulating the reproductive system by controlling gamete production and sex steroid hormone synthesis. How does luteinising hormone (LH) function in males? In males, luteinising hormone (LH) stimulates Leydig cells in the testes to produce testosterone, which is crucial for sperm formation, libido maintenance, and the development of secondary sexual characteristics. Elevated testosterone levels also exert negative feedback on the hypothalamus and pituitary to regulate hormone production. What is the function of follicle-stimulating hormone (FSH) in males? Follicle-stimulating hormone (FSH) promotes sperm production by acting on Sertoli cells in the testes and facilitates the synthesis of proteins necessary for steroid hormone action. It also produces inhibins, which specifically inhibit FSH secretion without affecting LH levels. How do oestrogens and progestins regulate the hypothalamic-pituitary-gonadal axis in females? In females, oestrogens and progestins provide both negative and positive feedback to the anterior pituitary and hypothalamus. Moderate oestrogen levels inhibit LH and FSH secretion, while high oestrogen levels, in the absence of progesterone, stimulate their release. What is the clinical significance of gonadotropin-releasing hormone (GnRH) in prostate cancer treatment? In prostate cancer, prolonged exposure to GnRH leads to desensitisation of gonadotrophs, reducing the release of LH and FSH and subsequently lowering testosterone production. This mechanism is exploited in treatment using long-acting GnRH analogues for medical castration, which can help shrink tumours driven by testosterone. Rate This Article