CENTRAL CONTROL OF PITUITARY SECRETION 



I02t 



tails technical difliculties. In recent work Donovan & 

 van der Werff ten Bosch (83, 85) found that electrical 

 stimulation of the anterior hypothalamus over periods 

 of 1 2 weeks failed to induce estrus in female ferrets 

 during the winter. Since lesions in the same sites in 

 anestrous ferrets brought them into heat, the possibil- 

 ity exists that FSH secretion is normally regulated by 

 an inhibitory neural mechanism and from the present 

 data it would seem more reasonable to see whether 

 electrical stimulation of the anterior hypothalamus 

 inhibited, rather than elicited, estrus. 



ACTH Secretion and Hypotlialamic Stimulation, de 

 Groot & Harris (72) and Hume & VVittenstein (188) 

 first reported that electrical stimulation of the hypo- 

 thalamus in the conscious animal resulted in a dis- 

 charge of AC^TH as shown by a lymphopenia in the 

 rabbit (72) and an eosinopenia in the dog (188). In 

 both these studies the remote control method of 

 stimulation was used. Later workers have confirmed 

 these results, using the eosinopenic response and 

 implanted electrodes witii leads through the skin in 

 the cat (5, 270) and in the monkey (271). The site in 

 the hypothalamus from which such responses are 

 obtained has been given as the posterior tuber 

 cinereum (72, 185, 270, 271), mammillary bodies 

 (72, 270, 271) and more anteriorly in the median 

 eminence (5, 185). Surrounding areas in the hypo- 

 thalamus did not evoke the response and neither did 

 direct stimulation of the pituitary sjland itself (72). 



TSH Secretion and Hypothalamic Stimulation. It is 

 claimed (73) that electroshocks applied diffusel)- to 

 the heads of guinea pis;s result in cytological signs of 

 thyroid activation and an increase in TSH in the 

 circulation within 30 min. More localized stimulation 

 of the hypothalamus was performed in rats and rab- 

 bits by Golfer (56) who found histological signs of 

 increased acti\'ity in the thyroid pro\iding stimulation 

 was applied for at least four i-hr. periods on each of 

 2 days. No optimum site for the response was found in 

 the hypothalamus, but control stimulation of the 

 thalamus or corpus callosum was without efifect. 



More recently (164, 165) electrical stimulation of 

 various areas in the hypothalamus and pituitary 

 gland has been carried out using the remote control 

 method for stimulation in unanesthctized rabbits, and 

 the rate of release of thyroidal I"' and the blood con- 

 centration of protein-bound I''" for assessing thyroid 

 activity (fig. 6). Out of 43 rabbits stimulated, 9 

 animals showed increased thyroid activity that ap- 

 peared in every way similar to that following an in- 

 jection of thyrotrophic hormone. A striking feature is 

 the finding that after adrenalectomy (with cortisone 



°/olOO 



FIG. 6. To show the effect of electrical stimulation of the 

 median eminence on the biological decay of thyroidal radio- 

 activity (I"') and on the blood level of FBI'-'', .\drenalectomized 

 and ovariectomized rabbit. Previous to adrenalectomy, stimu- 

 lation had resulted in thyroid inhibition. [From Harris, G. VV. 

 & J. W. W'oods, unpublished observations.] 



maintenance), 13 of 26 of the same animals showed a 

 clear-cut increase of thyroid function on stimulation. 

 Of these 13 animals, 10 had shown no thyroid response 

 before adrenalectomy; in the other 3 animals the re- 

 sponse was markedly increased after adrenalcctomv. 

 This change in response seems due to the removal of 

 the adrenal cortex since a) preliminary denervation 

 of the adrenals did not interfere with the effects of 

 adrenalectomy and b) administration of high doses of 

 cortisone to animals with an intact adrenal, in an 

 attempt to block AGTH discharge, often resulted in 

 positive ih\ roid response to stimulation which had not 

 been seen previously. Since administration of .\CTH 

 or compounds B, E or F has been shown to result in 

 diminished thyroid acti\it\ in the rabbit and other 

 forms, probably by inhibiting secretion of TSH, and 

 since electrical stimulation of the hypothalamus is 

 known to evoke discharge of .XGTH from the anterior 

 pituitary, it seems likelv that adrenalectomy is effec- 

 tive since it prevents any sudden rise in the blood con- 

 centration of adrenal steroids during the period of 

 stimulation. A noteworthy feature of these results was 

 the fact that hypothalamic stimulation could main- 

 tain an increased thyroid activ'ity in the presence of 

 an increa.sed blood concentration of PBI'". This 

 indicates that the influence of the central nervous 

 system can preponderate over the effects of the 'feed- 



