60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: Harris' neuroendocrine revolution: of portal vessels and self-priming

What is it about?

Geoffrey Harris, while still a medical student at Cambridge, was the first researcher (1937) to provide experimental proof for the then tentative view that the anterior pituitary gland was controlled by the CNS. The elegant studies carried out by Harris in the 1940s and early 1950s, alone and in collaboration with John Green and Dora Jacobsohn, established that this control was mediated by a neurohumoral mechanism that involved the transport by hypophysial portal vessel blood of chemical substances from the hypothalamus to the anterior pituitary gland. The neurohumoral control of anterior pituitary secretion was proved by the isolation and characterisation of the ‘chemical substances’ (mainly neuropeptides) and the finding that these substances were released into hypophysial portal blood in a manner consistent with their physiological functions. The new discipline of neuroendocrinology – the way that the brain controls endocrine glands and vice versa – revolutionised the treatment of endocrine disorders such as growth and pubertal abnormalities, infertility and hormone-dependent tumours, and it underpins our understanding of the sexual differentiation of the brain and key aspects of behaviour and mental disorder. Neuroendocrine principles are illustrated in this Thematic Review by way of Harris’ major interest: hypothalamic–pituitary–gonadal control. Attention is focussed on the measurement of GnRH in hypophysial portal blood and the role played by the self-priming effect of GnRH in promoting the onset of puberty and enabling the oestrogen-induced surge or pulses of GnRH to trigger the ovulatory gonadotrophin surge in humans and other spontaneously ovulating mammals.

Featured Image

Why is it important?

This paper outlines the history of "Neuroendocrinology", the discipline concerned with the way that the brain controls the key hormones of the body, and in turn the way in which hormones affect brain function. The paper focuses on the mechanism by which the brain controls the synthesis and release of pituitary hormones and in particular the gonadotrophins that trigger ovulation. Nerve cells in the "hypothalamus" at the base of the brain release a chemical ("peptide") termed "gonadotrophin releasing hormone (GnRH)" into an exquisite set of vessels that transport blood from the hypothalamus to the anterior pitiuitary gland where GnRH stimulates the synthesis and release of the gonadotrophins. Ovulation is caused by the surge release of GnRH, which in turn is triggered by a surge of estrogen, released from the ovary. This "positive feedback" effect of estrogen is amplified several fold by the "self-priming" effect of GnRH: that is, GnRH enhances the response of the anterior pituitary gland to itself. The self priming effect of GnRH also explains how small frequent pulses of GnRH could also induce a gonadotrophin surge. The ovulatory surge of gonadotrophin is essential for the reproduction of most mammals including the human. The self-priming effect of GnRH plays a pivotal role in the onset of puberty. An early, erroneous, onset of GnRH pulses lead to precocious puberty. The principles of this system and especially GnRH self-priming are used in in-vitro fertilization in the human and other mammals, livestock production and fish-farming. GnRH and its analogues administered continuously is used in the control of hormone-dependent cancers such as breast and prostate.

Perspectives