It has been known since the time of Heape (1905) that the isolated female rabbit does not ovulate spontaneously but requires sensory stimuli, normally associated with coitus, to excite follicular rupture. The evidence indicates that the act of mating excites a nervous reflex pathway passing to the hypothalamus, which in turn stimulates the anterior pituitary gland to release increased amounts of luteinizing hormone (LH). Harris (1937, 1948), Haterius & Derbyshire (1937) and Markee, Sawvyer & Hollinshead (1946) all found that electrical stimulation of the hypothalamus in the isolated female rabbit was followed by ovulation.The mechanism by which the hypothalamus regulates gonadotrophin secretion by the anterior pituitary gland seems to involve the liberation of a humoral agent from the nervous tissue of the median eminence of the tuber cinereum into the hypophysial portal vessels, and thereby the transmission of this agent to the anterior pituitary gland. Evidence relating to this view is as follows (see Harris, 1955, for detailed discussion): (1) It is very doubtful whether nerve fibres, other than vasomotor, exist in the adenohypophysis. (2) All major vertebrate groups possess a vascular system carrying blood from the median eminence to the adenohypophysis (Green, 1951). (3) The evidence that electrical stimulation of the hypothalamus evokes ovulation in the rabbit, whereas similar stimulation applied directly to the anterior pituitary gland itself is ineffective (Markee et al. 1946;Harris, 1948), is compatible with the view of humoral stimulation of the gland cells. (4) Permanent interruption of the hypophysial portal vessels (by pituitary stalk section or pituitary transplantation) results in a permanent and severe loss of ovarian activity; temporary interruption followed by regeneration of the portal vessels is often associated with a post-operative return of normal ovarian function.

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Harris & Woods (1958) The ideal method of measuring the activity of endocrine glands appears to be to measure the rate of secretion of hormone into the blood stream; that is, to measure the hormone content of the arterial blood to, and the venous blood from, the gland and the rate of blood flow through it. Various attempts which approximate to the ideal method, in that measurements were made of the hormone content of the glandular venous blood, have been reported (adrenal medulla, Satake, Sugawara & Watanabe, 1927; Brucke, Kaindl & Mayer, 1952; Duner, 1953; Folkow & von Euler, 1954;Satake, 1955; adrenal cortex, Vogt, 1943 adrenal cortex, Vogt, , 1944Bush, 1951;Nelson & Hume, 1955;Reif & Longwell, 1958; neurohypophysis, Andersson, 1951; Ginsburgh & Heller, 1953;Fitzpatrick & Hughes, 1957; testis, Samuels, 1957). Soderberg (1958) cannulated thyroid veins in anaesthetized cats and rabbits and presented clear results on the rate of thyroid blood flow, rate of iodine uptake and rate of secretion of labelled thyroid hormone. The techniques developed by Soderberg were applicable to observations extending over periods of seconds to minutes and were used to determine the effects on thyroid blood flow and activity of interference with the nerve supply to the gland or the administration of various substances.

SUMMARY1. Intrapituitary infusions of extracts made from the median eminence of various species at different ages were found to excite secretion of gonadotrophic hormone as shown by consequent ovulation, presumably due to their content of luteinizing hormone-releasing factor (LRF).2. Extracts from very immature animals (e.g. new-born rabbits and rats; 1-2-month-old calves) were found to be highly active with regard to LRF content.3. Extracts from foetal rabbits at 20 days of gestation showed no evidence of containing LRF.4. It is suggested that (a) LRF may have a trophic action upon the anterior pituitary gland during the pre-puberal phase of life, and that (b) the first formation of LRF coincides with the development of the primary plexus of the pituitary portal system.