Introduction
This topic covers the hormonal axes that control reproduction, growth and milk production, together with the two hormones stored in the posterior pituitary. Each axis follows the same pattern: a hypothalamic releasing hormone acts on the anterior pituitary, which releases a tropic hormone that acts on a target gland or tissue, and the end products feed back on the hypothalamus and pituitary.
The hypothalamic-pituitary-gonadal (HPG) axis
Gonadotropin-releasing hormone (GnRH)
- GnRH is a decapeptide made by hypothalamic neurons and secreted in pulses into the hypophyseal portal system.
- Pulsatile release is essential for normal gonadotropin secretion. Continuous GnRH desensitises the pituitary receptor, which is why long-acting GnRH agonists are used therapeutically, for example in prostate cancer.
- The GnRH receptor is coupled to Gq. It activates phospholipase C, which produces IP3 and DAG and raises intracellular calcium.
FSH and LH
- Follicle-stimulating hormone (FSH) and luteinising hormone (LH) are glycoprotein heterodimers that share an alpha subunit and differ in the beta subunit.
- FSH acts on Sertoli cells, which support spermatogenesis and produce inhibin B, and on granulosa cells, which support follicle growth and produce oestradiol.
- LH acts on Leydig cells to make testosterone and on ovarian theca cells to supply androgens to the granulosa cells. In women, a midcycle LH surge triggers ovulation and luteinisation.
Feedback control
- Negative feedback by testosterone, oestradiol and inhibin reduces GnRH and gonadotropin secretion.
- Positive feedback occurs when oestradiol stays high for several days during the follicular phase. It triggers the midcycle LH surge.