I024 



HANDBOOK OF PH^■SIOLOC;V 



NEUROPHYSIOLOGY 11 



thalamus. Greer (130) found the thyroid glands of 

 rats with such lesions (even treated with propylthio- 

 uracil) to be slightly smaller than untreated controls. 

 Bogdanove et al. (36) found that hypothalamic lesions 

 in rats resulted, in a few cases, in thyroid atrophy. 

 Ganong et al. (115) reported that in 5 out of 23 dogs 

 hypothalamic lesions resulted in a reduction in I'" 

 uptake by the thyroid and histological signs of thyroid 

 atrophy. These five animals were found to possess 

 lesions in the anterior end of the median eminence. 

 More recently D'Angelo & Traum (66) have demon- 

 strated both a thyroid atrophy, and a reduction (to 

 aljout one-half normal) of the TSH concentration in 

 the blood, following anterior hypothalamic lesions in 

 rats. It seems clear that the reduction of thyroid activ- 

 ity is not as great as that following hypophysectomy 

 which confirms the results di.scussed above obtained 

 by pituitary stalk section. 



b) Site of effective lesions. There is general agreement 

 that the efTective site lies in the anterior hypothalamus. 

 Greer (130) states, "The impression gained so far, 

 however, is that the area is anterior to the ventro- 

 median nucleus and lies along or near the ventral 

 surface of the hypothalamus, possibly near the ventral 

 extension of the supraopticohypophysial tract." This 

 site has been confirmed in rats (35) and dogs (i 15). 



c) ^Feed-back' mechanism of thyroid hormone. The fact 

 that large anterior hypothalamic lesions in the rat 

 (35, 130, 131) prevent the usual goitrogenic response 

 to propylthiouracil feeding and also prevent com- 

 pensatory hypertrophy in partially thyroidectomized 

 rats suggests that the hypothalamus is involved in 

 the stimulus to increased TSH secretion in response 

 to a lowered concentration of thyroid hormone in the 

 blood. On the other hand, the evidence that adminis- 

 tration of exogenous thyroxine still inhibits thyroid 

 activity in the pituitary stalk-sectioned rabbit (47), or 

 in the rabbit with the pituitary gland transplanted to 

 the anterior chamber of the eye (345), suggests that 

 an increased blood level of thyroxine may act directly 

 on the pituitary gland. This latter hypothesis is sup- 

 ported by the findings of von Euler & Holmgren (344) 

 who found that injection of minute doses of thyroxine 

 into the pituitary gland inhibited thyroid function, 

 whereas similar injections into the hypothalamus did 

 not. These curious findings are comparable with 

 those regarding the feed-iiack mechanism of adrenal 

 steroids. 



TARGET GLAND ACTIVITY AND ELECTRICAL STIMULA- 

 TION OF HYPOTHALAMUS. Gonadotropliic Secretion and 

 Ily/iothalamic Stimulation. The original experiment 



indicating that electrical stimulation of the nervous 

 system might result in discharge of anterior pituitary 

 hormone was made by Marshall & Verney (225) who 

 showed that diffuse electrical stimuli applied to the 

 head or lumbar spinal cord of rabbits resulted in dis- 

 charge of gonadotrophic hormone and therefore ovu- 

 lation and pseudopregnancy in a large proportion of 

 animals. Similar results were later obtained by Harris 

 (147) in rats in which a state of pseudopregnancy was 

 induced by cranial stimulation. In an attempt to 

 delimit the neural structure involved Harris (148) 

 applied localized electrical stimulation to various 

 regions of the hypothalamus and pituitary gland in 

 anesthetized rabbits and found that stimulation of the 

 tuber cinereum, posterior hypothalamus or pituitary 

 gland directly might result in ovulation or the forma- 

 tion of cystic and hemorrhagic follicles. These results 

 were soon confirmed, in the main, by Haterius & 

 Derbyshire (169) who placed the effective hypotha- 

 lamic site more anteriorly. Some 9 years after these early 

 results Markee et al. (218) found that stimulation ol 

 the tuber cinereum in the rabbit evoked discharge of 

 luteinizing hormone and ovulation but that direct 

 stimulation of the pituitary gland failed to give this 

 response unless there were signs of spread of the 

 stimulus. Perhaps the most satisfactory technique for 

 such studies is some variation of the remote control 

 method, whereby a coil, leads and electrodes are im- 

 planted subcutaneously so that after the animal has 

 recovered from the initial operation and is conscious 

 it may be stimulated by inducing the voltage from an 

 external field coil. With this technique the same site in 

 the nervous system may be stimulated in repeated 

 experiments and the results in any one animal thereby 

 confirmed several times. By its use it was found (151) 

 that stimulation of the tuber cinereum for as short a 

 time as 3 min. might result in a full ovulation response 

 but that similar stimuli applied to the anterior pitui- 

 tary, pars intermedia or infundibular stem for periods 

 of up to 7I2 hr. were without effect in causing 

 gonadotrophic stimulation. Since the pituitary gland 

 thus appears inexcitaijle to direct electrical stimula- 

 tion, these results called attention to the possibility 

 that the hypothalamus normally excites anterior 

 pituitary secretion by some humoral mechanism (151, 

 218). 



The above work made use of the ovulation reflex 

 in the rabbit as a quick indicator of discharge of 

 luteinizing hormone. Stimulation of the hypothalamus 

 with observation of changes indicative of secretion of 

 FSH or luteotrophic hormone have rarely been made 

 since the slow nature of the phenomena involved en- 



