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

  1. George Fink
  1. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, Genetics Lane, Parkville, Victoria 3010, Australia
  1. Correspondence should be addressed to G Fink; Email: george.fink{at}florey.edu.au; georgefink1{at}hotmail.com
  1. Figure 1

    High-power view through a dissecting microscope of the hypophysial portal vessels on the anterior surface of the pituitary stalk (left) of an anesthetised rat. The portal vessels (veins) arise from the primary capillary bed on the median eminence (pink area to the left) and fan out over the anterior pituitary gland (right) at the pituitary stalk junction to the right. The tubero-infundibular artery, a branch of the superior hypophysial artery, can be seen arching across the top of the stalk–pituitary junction, where it enters the anterior pituitary gland. This artery passes through the anterior pituitary gland to supply arterial blood to the neurohypophysis. Reproduced from Handbook of Neuroendocrinology, Fink G, Neural control of the anterior lobe of the pituitary gland (pars distalis), pp 97–138, copyright (2012), with permission from Elsevier. Note: The contentious history of the discovery and function of the hypophysial portal vessels is detailed in chapter 2 of Harris' (1955) monograph, to which the interested reader is referred. Popa & Fielding (1930, 1933), who first discovered the hypophysial portal system, posited that the direction of blood flow was centripetal: that is, from the anterior pituitary gland towards the hypothalamus. The direction of portal vessel blood flow (centrifugally from the hypothalamus to the anterior pituitary gland) was ultimately resolved by microscopic visualisation of the vessels in the living anaesthetised rat (Green & Harris 1949). In fact, Nobel Laureate (1947) Bernado Houssay and his team had reported the centrifugal direction of portal vessel blood flow in the living toad (Houssay et al. 1935), but because their publication was in French, it was ignored until the late 1940s. The functional importance of the hypophysial portal vessels involved Harris in a conflict with the influential Sir Solly Zuckerman, who, on the basis of studies in the ferret, challenged the neurohumoral hypothesis of anterior pituitary control. The debate between Zuckerman and Harris was the subject of letters to Nature (Thomson & Zuckerman 1953, Donovan & Harris 1954). Before publishing his 1954 reply to Zuckerman, Harris submitted a draft of his letter to the regents of the Maudsley Hospital. After several months, the regents gave Harris permission to publish, but they cautioned him that if he did so, he would 'have a powerful enemy for life' (Geoffrey Harris, 1971, personal communication).

  2. Figure 2

    Electromicrograph (×13 200) of the external layer of the median eminence of a rat at the first postnatal day. Note the high density of nerve terminals around part of a primary portal capillary vessel (P), which is fenestrated (F). Note also the large number of agranular and granular vesicles in the nerve terminals. These vesicles contain the packets (quanta) of neurohormone or neurotransmitter that are released upon nerve depolarisation as a consequence of action potentials. The neurohormones are released into the perivascular space, and from there, they move rapidly into portal vessel blood for transport to the pituitary gland. This arrangement is typical of the neurohaemal junctions found in the several circumventricular organs of the brain (see text). E, endothelial cell; F, fenestration; G, glial process; P, portal vessel; PVC, perivascular cell; PVS, perivascular space. Reproduced from Fink G & Smith GC 1971 Ultrastructural features of the developing hypothalamo–hypophysial axis in the rat: a correlative study. Zeitschrift fur Zellforschung und Mikroskopische Anatomie 119 208–226, with kind permission from Springer Science and Business Media.

  3. Figure 3

    Mean±s.e.m. concentrations of LHRH (GnRH) in hypophysial portal plasma collected from female rats that were anesthetised with alphaxalone at various stages of the oestrous cycle. For most of the cycle, the concentrations of GnRH are low, but just before and during the surge of LH (dashed line), there is a surge of GnRH. The volumes of portal blood collected are shown in the lower panel. Reproduced from Sarkar DK, Chiappa SA, Fink G & Sherwood NM 1976 Gonadotropin-releasing hormone surge in pro-oestrous rats. Nature 264 461–463, with permission from Macmillan Journals.

  4. Figure 4

    Mean±s.e.m. concentrations of LHRH (GnRH) in hypophysial portal plasma and volumes of portal blood collected at various times (indicated at top) on the expected day of pro-oestrus. The animals were either intact (filled bars) or ovariectomised at 1000–1100 h of dioestrus and given an s.c. injection of oil (open bars), 2.5 mg progesterone (diagonally hatched bars) or 10 μg oestradiol benzoate (cross-hatched bars). Values below the bars refer to the total number of samples of each time/number of samples in which GnRH was not detectable. The GnRH surge was abolished by ovariectomy and was re-established by treatment at the time of ovariectomy with oestrogen but not progesterone. Reproduced, with permission, from Sarkar DK & Fink G 1979b Effects of gonadal steroids on output of luteinizing hormone releasing factor into pituitary stalk blood in the female rat. Journal of Endocrinology 80 303–313.

  5. Figure 5

    Changes in pituitary responsiveness to LHRH (GnRH) during the oestrous cycle of the rat. The figure shows the mean±s.e.m. pre-injection concentrations (dashed line) and mean maximal increments (continuous line) in plasma LH concentrations (ng NIH-LH-S13/ml) in animals that were anaesthetised with sodium pentobarbitone 30–60 min before the i.v. injection of 50 ng LHRH/100 g body weight at different stages of the oestrous cycle. Reproduced, with permission, from Aiyer MS, Fink G & Greig F 1974a Changes in sensitivity of the pituitary gland to luteinizing hormone releasing factor during the oestrous cycle of the rat. Journal of Endocrinology 60 47–64.

  6. Figure 6

    Electromicrographs (×10 000) of immunoidentified gonadotrophs from the anterior pituitary glands of hypogonadal mice. The glands were pre-incubated for 2 h in medium alone and then incubated for two successive periods of 1 h each either in medium alone (A) or 8.5 nmol GnRH/1 of medium (B). A marginal zone, which is indicated by the line and arrows, has been arbitrarily defined as the region of the cytoplasm within 500 nm of the plasmalemma. In (A), the secretory granules are generally distributed in the cytoplasm, but in (B), there is a concentration of granules within the marginal zone. Reproduced, with permission, from Lewis CE, Morris JF, Fink G & Johnson, M 1986 Changes in the granule population of gonadotrophs of hypogonadal (hpg) and normal female mice associated with the priming effect of LH-releasing hormone in vitro. Journal of Endocrinology 109 35–44.

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