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

2015 ◽  
Vol 226 (2) ◽  
pp. T13-T24 ◽  
Author(s):  
George Fink

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 andvice 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.

1975 ◽  
Vol 65 (3) ◽  
pp. 439-445 ◽  
Author(s):  
G. FINK

SUMMARY The responsiveness of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) was tested in rats exposed to constant light. At a dosage of 50 ng LH-RF/ 100 g body wt the mean maximal increments in plasma LH and FSH were similar to those at 10.00 h of pro-oestrus. The increments in the plasma gonadotrophins at dosages of 500 and 1000 ng LH-RF/100 g body wt did not differ significantly from those at 250 ng LH-RF/ 100 g body wt. These findings suggest that, in contrast to rats which exhibit regular oestrous cycles, the preovulatory (post-coital) release of LH in rats exposed to constant light may depend almost entirely on the release of a relatively large amount of LH-RF into hypophysial portal vessel blood. Whereas in pro-oestrous animals a relatively small fraction of the readily releasable pool of LH is released during the spontaneous preovulatory surge, in rats exposed to constant light most releasable LH appears to be discharged during the reflex preovulatory surge of this hormone. The concentrations of radioimmunoassayable FSH in blood samples withdrawn before the injection of LH-RF support the view that FSH secretion in the rat is increased by constant exposure to light.


1974 ◽  
Vol 76 (3) ◽  
pp. 417-430 ◽  
Author(s):  
Oddvar Næss ◽  
Arne Attramadal

ABSTRACT [1,2-3H] testosterone was given intramuscularly to castrated adult male and female rats. The concentration of radioactivity in the anterior pituitary gland, hypothalamus, preoptic area, brain cortex, ventral prostate and muscle tissue was measured at different time intervals. In the ventral prostate a preferential concentration and retention of radioactivity was recorded. In the anterior pituitary, hypothalamus, preoptic area and brain cortex, however, the maximum uptake was observed 7½ min after the injection of the hormone. Thereafter the radioactivity rapidly declined. Non-labelled testosterone was found to compete with the radioactive testosterone for the binding sites in the anterior pituitary, hypothalamus and preoptic area. High doses of non-labelled testosterone caused a slight, and statistically insignificant reduction of the radioactivity in the brain cortex. The concentration of radioactivity in the muscle tissue was not affected by any of the doses of non-radioactive testosterone given. Filtration of serum on Sephadex G-25 columns showed that considerable amounts of radioactivity were associated with macromolecules. Therefore in order to get a valid record of the binding of androgens to the specific molecules of the target cells, perfusion of the vascular system was essential. In vivo and in vitro experiments revealed that considerable amounts of radioactive material were bound to macromolecules in the cytosol fractions of the anterior pituitary gland, hypothalamus, preoptic area and brain cortex. Thus for the first time a binding of androgens by macromolecules in the cytosol fraction of the preoptic area and brain cortex has been found. Since association of androgens with plasma constituents can be excluded, the radioactive material is most likely bound to specific binding molecules present in the target cells of the anterior pituitary gland, hypothalamus, preoptic area and the brain cortex.


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