CENTRAL CONTROL OF PITUITARY SECRETION 



1023 



obtained by Flerko (103), and to those observed in 

 young children who develop hypothalamic tumors 

 and precocious puberty. The literature on these latter 

 cases is reviewed by Weinberger & Grant (347) and 

 Bauer (19). The experimental production of prema- 

 ture secretion of FSH, and precocious puberty, by 

 damage to the hypothalamus has been observed by 

 Gaupp (iig) in the rabbit and Dono\an & \an der 

 Werff ten Bosch (84) in the rat. One puzzling finding 

 of these results is that lesions in the anterior hypo- 

 thalamus (84) seem responsible for the release of 

 FSH secretion in the experimental animal, whereas 

 the general finding in clinical studies is that tumors in 

 the region of the mammillary bodies are more often 

 associated with pubertas praecox in the human. It 

 may be anticipated that this important field will re- 

 ceive much attention in the next few years. 



ACTH Secretion and Hypothalamic Lesions. There is 

 good evidence that hypothalamic lesions will markedly 

 reduce, or abolish, the increased discharge of ACTH 

 that normally follows conditions of stress, de Groot & 

 Harris (72) found that bilateral electrolytic lesions in 

 the posterior part of the tuber cinereum or in the 

 mammillary body might aljolish the lymphopenia 

 produced by emotional stress in rabbits, and Hume & 

 Wittenstein (188) found that the eosinopenia following 

 stress in dogs was prevented by paramedian lesions in 

 the anterior hypothalamus. Hume (185, 186) has 

 more recently reported that lesions in the anterior 

 part of the median eminence are most effective in 

 abolishing the AC:TH response to stress. Confirmatory 

 results have been obtained in other forms, such as 

 rats (6, 90, 233, 318), cats (206, 270) and monkeys 

 {271). 



a) Lesions and resting rate of ACTH secretion. Hypo- 

 thalamic lesions have been reported as having little 

 effect on adrenal size (116, 206, 233 j although the 

 stress-induced release of ACTH was blocked in some 

 animals. This would indicate that hypothalamic 

 lesions do not affect the resting rate of secretion of 

 ACTH. However, adrenal atrophy following hypo- 

 thalamic damage has been seen in a few animals (36) 

 and was reported (234) to follow interruption of the 

 supraopticohypophysial tract in rats in wiiich the 

 water intake per day was increased to 100 to 200 ml. 

 Greer & Erwin (133) have recently reported that 

 some adrenal atrophy occurs in the rat after lesions of 

 the median eminence. Since gonadal and thyroidal 

 atrophy may follow hypothalamic lesions it would ije 

 somewhat surprising if further observations showed 

 normal adrenals in the presence of similar lesions. 



b) Types of stress. Destruction of areas in the median 



eminence or posterior tuber cinereum has been found 

 to abolish the stress response to epinephrine, surgical 

 trauma or unilateral adrenalectomy (116, 187, 233, 

 270, 271). These findings are in apparent conflict 

 with the observations that complete separation of the 

 pituitary from the hypothalamus, by stalk section or 

 transplantation, is compatible with ACTH responses 

 to the same stimuli. A possible explanation has been 

 suggested by McCann (233). ''A neurohumoral sub- 

 stance is released in the median eminence which 

 normally traverses the hypophysial portal vessels and 

 causes release of ACTH. In cases of severe stress, 

 sufficient amounts of this substance may be released 

 to activate the anterior lobe via the general circula- 

 tion." On this view the response of the transplanted or 

 stalk-cut pituitary would not depend on the nature 

 but on the relative intensity of the stress stimuli which 

 would in all cases act through the hypothalamus. 



c) Site of ejfective lesions. There is no general agree- 

 ment as to the site of lesions which result in blockade 

 of the ACTH discharge following stress. Some workers 

 place the efTective site in the posterior tuber cinereum 

 and maminillary region (72, go, 270, 271, 318) while 

 others give the eff'ective site as median eminence (206), 

 anterior median eminence (186, 187) or in the path of 

 the supraopticohypophysial tract (234, 235). Such 

 discrepancies as these are perhaps not surprising in 

 view^ of the complex, and largely unknown, anatomy 

 of the tracts in the hypothalamus and the fact that 

 many nervous reflex paths may initiate the ACTH 

 response to different types of stress stimuli. 



d) 'Feed-back'' mechanism. It is well known that an 

 increased blood level of adrenal steroids inhibits 

 ACTH secretion and a decreased blood level (after 

 unilateral adrenalectomy) stimulates ACTH secre- 

 tion. Ganong & Hume (i 16) on dogs and Fulford & 

 McC^ann (113) on rats have both shown that the com- 

 pensatory hypertrophy after unilateral adrenalectomy 

 is abolished by lesions in the anterior median emi- 

 nence. However, Ganong & Hume (117) found that 

 median eminence destruction in the dog did not pre- 

 vent adrenal atrophy following administration of 

 cortisone. It is of interest that these superficially dis- 

 cordant findings are similar to those regarding the 

 feed-ljack mechanism of thyroid hormone (see below). 



TSH Secretion and Hvpothalamic Lesions. Many 

 workers have now reported that lesions in the hypo- 

 thalamus may interfere with the normal secretion of 

 TSH (35, 36, 66, 115, 130, 131, 133, 278). 



a) Lesions and resting rate of TSH secretion. There can 

 be little doubt that the normal resting rate of secretion 

 of TSH is reduced by lesions in the anterior hypo- 



