CENTRAL CONTROL OF PITUITARY SECRETION 



I03I 



These results were confirmed in the monkey, Ijoth bs' 

 placing electrolytic lesions, and later by Magoun et 

 al. (215) by pituitary stalk section. The important 

 contribution of this group was the demonstration 

 that the hypothalamus-neurohypophysis functions as 

 a unit and that it is the supraopticohypophysial tract 

 which is the important connecting link between the 

 two structures. It is on the basis of these studies that 

 the concept that neurohypophysial activity is com- 

 pletely dependent on its innervation may be con- 

 sidered established. 



The obvious experimental corollary to the work of 

 Ranson and his group — that electrical stimulation of 

 the supraopticohypophysial tract elicits increased re- 

 lease of ADH — has been most clearly established by 

 using unanesthetized animals (149). With the remote 

 control method of stiixiulation it has been possible to 

 demonstrate that a release of ADH, with a resultant 

 inhibition of water diuresis, follows electrical stimula- 

 tion of the supraopticohypophysial tract in the hypo- 

 thalamus, median eminence, infundibular stem or 

 infundibular process. The duration of the antidiuretic 

 response could be correlated with the intensity of the 

 stimulus, and the responses in any one animal to a 

 given stimulus remained remarkably constant over 

 periods of weeks or months. The fact that the supra- 

 opticohypophysial tract may be stimulated elec- 

 trically, with typical 'secretomotor' responses, makes 

 it seem very likely that these fibers conduct nerve 

 impulses and regulate neurohypophysial activity as 

 does the secretomotor innervation of other glands. 



The idea that neurohypophysial activity is affected 

 by the composition of the blood, especially by changes 

 in the osmotic pressure of the blood, was put forward 

 by Klisiecki et al. (200, 201 ) to explain the mechanism 

 of a water diuresis. They suggested that ingestion and 

 absorption of water results in a decreased osmotic 

 pressure of the blood and consequent inhibition of the 

 secretion of antidiuretic hormone with a resultant 

 diuresis which begins after the hormone already in 

 the blood stream has been removed or inactivated. 

 The effect of increasing the osmotic pressure of carotid 

 blood on neurohypophysial activity has been investi- 

 gated in detail by Verney and the results reviewed 

 (338, 339). \'erney found that an injection of isotonic 

 solution of sodium chloride into the carotid artery, or 

 of hypertonic solutions (up to 20 cc of 0.343 ^ NaCl 

 in 20 sec.) intravenously did not inhibit a water 

 diuresis. However, injection of similar hypertonic so- 

 lutions into the carotid artery resulted in marked 

 inhibition in the course of a water diuresis, a response 



that very closely simulated that following intravenous 

 injection of posterior pituitary extract. The pituitary 

 origin of the response was established b\- the observa- 

 tion that surgical removal of the neural lobe of the 

 pituitary reduced the response to about 10 per cent 

 of that obtained previously. More prolonged infusions 

 of sodium solution were then studied to obtain infor- 

 mation regarding the smaller and longer-lasting 

 changes in osmotic pressure of the blood likely to occur 

 in the normal animal. In this connection results of 

 experiments involving 10- and 40-min. infusions of 

 hypertonic saline showed that a rise of only i per cent 

 in the osmotic pressure of aortic blood would probably 

 reduce a water diuresis to only 10 per cent of the max- 

 imum rate of urine output, a response which would 

 correspond to a release of about i ;uu per sec. of an- 

 tidiuretic substance. The site of the osmoreceptor 

 mechanism is not clearly established. There are data 

 indicating that it is located in the territory of supply 

 of the internal carotid artery and that it lies in the 

 diencephalon but not in the neurohypophysis (194). 

 The most probable site is the supraoptic nuclei, a 

 site suggested by the extremely vascular nature of 

 these cell groups and by the specialized intracellular 

 vesicles found there (193). 



Emotional stress seems a potent factor in eliciting 

 secretion of ADH. Rydin & Verney (289) investi- 

 gated the mechanism whereby forced running in dogs 

 evoked an antidiuretic response. They found that if 

 animals were repeatedly exercised the inhibitory re- 

 sponse on urine flow progressively diminished to final 

 extinction, and for this and other reasons suggested 

 that it was not the exercise per se, but the emotional 

 accompaniment, that was the effective stimulus. From 

 experiments involving kidney and adrenal denerva- 

 tion it was concluded that the renal response to 

 emotional stress is due to some agent humorally con- 

 ducted to the kidney, and that the agent was not 

 epinephrine but possiljly antidiuretic hormone. This 

 view was put beyond doubt b)' the findings of O'Con- 

 nor & Verney (251) and O'Connor (250) that removal 

 of the posterior lobe of the pituitary or section of the 

 supraopticohypophysial tract greatly reduced the 

 antidiuretic response to emotional stimuli. It seems 

 that stimuli which are calculated to give rise to 

 emotional excitement activate nervous pathways to 

 the supraoptic nuclei which in turn evoke the release 

 of ADH from the neurohypophysis. The anatomy of 

 any afferent pathways to the supraoptic nuclei is 

 unknown. The studies of Pickford and others, how- 

 ever, indicate that at least some of these fibers are 

 cholinergic in nature (87, 98. 261-263). 



