60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: Geoffrey Harris and my brush with his unit

Abstract

Geoffrey Harris is chiefly known for his demonstration of the control of the pituitary gland by the portal vessels coming from the hypothalamus. This does not do justice to his extraordinary contribution to biology. Harris' life's work was central in demonstrating the brain/body interactions by which animals and humans adapt to their environment, and above all the control of that most crucial and proximate of all evolutionary eventsreproduction. In this brief review, I have tried to put Geoffrey Harris' work in the context of the scientific thinking at the time when he began his work, and above all, the contribution of his mentor, FHA Marshall, on whose towering shoulders Harris rose. But this is mainly my personal story, in which I have tried to show the debt that my work owed to Harris and especially to my dear friend, the late Keith Brown-Grant in Harris' team. I myself was never an endocrinologist, but over a short period in the early 1970s, under the influence of such inspirational mentors, and using purely anatomical methods, I was able to demonstrate sexual dimorphism and hormone-dependent sexual differentiation in the connections of the preoptic area, regeneration of the median eminence, the ultrastructure of apoptosis, the requirement for the suprachiasmatic nuclei in reproductive rhythms, the existence of non-rod or cone photoreceptors in the albino rat retina and, later, the expression of vasopressin by solitary (one in 600) magnocellular neurons in the polydipsic di/di Brattleboro mutant rat; this phenomenon was subsequently shown to be due to aC1 reading frameshift. I end this brief overview by mentioning some of the abiding and fascinating mysteries of the endocrine memory of the brain that arise from Harris' work on the control of the endocrines, and by pointing out how the current interest in chronobiology emphasises what a Cinderella the endocrine mechanisms have become in current brain imaging studies.

Parallel trajectories in the discovery of the SCN‐OVLT and pituitary portal pathways: Legacies of Geoffrey Harris

“…It is widely accepted that, before Harris's work, it was not known how the brain communicated with the endocrine system 13–21 . It was well appreciated, however, that external stimuli, such as environmental cues related to seasons and availability of food and water, influenced hormones and behavior.…”

NeuroImmunoEndocrinology: A brief historic narrative

“…66 For a detailed and sharp review on his works, the reader can consult 60 Years of Neuroendocrinology published in the Journal of Endocrinology in 2015. [65][66][67][68][69][70] In 1977 Schally and Guillemin were awarded the Nobel Prize in physiology and their demonstrations became the hallmark of experimental and clinical neuroendocrinology. 63,65,66,68 In the decade after, glucocorticoid receptors in the brain and limbic system were first described by Bruce McEwen and became a fundamental contribution to neuroendocrinology science.…”

“…Later on he visited other laboratories across Europe synthetized some analogues and started clinical trials in patients with endocrine tumors 66 . For a detailed and sharp review on his works, the reader can consult 60 Years of Neuroendocrinology published in the Journal of Endocrinology in 2015 65–70 …”

New Insights into the Hypothalamic-Pituitary-Thyroid Axis

“…Roger Guillemin (1) The discovery of thyrotropin releasing hormone (TRH) in 1969 not only vindicated many years of hard work within the paradigm of a hypothalamic neurohormonal control of adenohypophysis secretion, but it was the most heuristic event in establishing the science of neuroendocrinology (1)(2)(3). It was the unequivocal demonstration of Geoffrey Harris' theory (1955) that the capillary network from the median eminence does not flow into the general circulation, but is conveyed by tiny blood vessels that discharge into the pituitary stalk, subsequently terminating in a second capillary network in the anterior pituitary gland (4). Harris postulated that this portal system provides a link via which shorter range hypothalamic hormones are transported to the anterior pituitary where they stimulate the secretion of anterior pituitary hormones into the systemic circulation.…”