PHYSIOLOGY OF ANTERIOR HYPOPHYSIS 



279 



3. Lesions in the H ypothahnnus 



The puzzling clinical association of le- 

 sions in or trauma to the base of the brain 

 in the region of the diencephalon and dis- 

 orders of the reproductive system set work- 

 ers to probing this area of the brain in 

 experimental animals as long ago as the 

 turn of the century (for review of the early 

 literature and critical analysis of the evi- 

 dence, see Anderson and Haymaker, 1948a, 

 b). Clinical or experimental lesions, de- 

 stroying much of the hypothalamus but 

 leaving the hypophysis intact, ordinarily 

 resulted in genital atrophy accompanied by 

 obesity (Frohlich type syndomej. Diabetes 

 insipidus did or did not ensue, depending 

 on whether the lesion disrupted hypotha- 

 lamic neural connections with the neuro- 

 hypophysis. A significant advance was 

 made in 1927 when Smith discovered quite 

 by accident that the chromic acid he was 

 injecting into the sella of rats to destroy 

 pituitary tissues led to extreme obesity 

 through damage to adjacent areas of the 

 brain. It remained for Cahane and Cahane 

 (1935, 1936) to dissociate in rats the se- 

 quelae of adiposity and deficiencies in the 

 reproductive system by means of carefully 

 placed lesions. Rats with lesions in the in- 

 fundibulum showed severe testicular or 

 ovarian atrophy and cessation of estrous 

 cycles with no obesity. Dey (1941, 1943a- 

 c), Dey, Fisher, Berry and Ranson (1940), 

 and Dey, Leininger and Ranson (1942) 

 were among the first to use stereotaxic in- 

 strumentsJBr a major study of the effect of 

 bilaterally placed hypothalamic lesions on 

 the reproductive organs and sexual behav- 

 ior. They were able by this means to pro- 

 duce two distinct categories of sexual re- 

 sponse in female guinea pigs. (1) Animals 

 with lesions in the median eminence ex- 

 hibited ovarian atrophy and loss of all re- 

 productive functions. (2) Animals with le- 

 sions in the anterior hypothalamus remained 

 in continuous estrus and the ovaries were 

 filled with large Graafian follicles. The le- 

 sions in the anterior hypothalamus seemed 

 to interfere with the release of LH. By 

 present thinking it is likely that the secre- 

 tion of LH continued at a low level but that 

 the reflex arc for acute release at the ap- 

 propriate time in the cycle was interrupted. 



In guinea pigs lesions elsewhere in the hy- 

 pothalamus produced no impairment of 

 gonadal functions, yet some of the animals 

 did not mate. 



Essentially similar findings and some- 

 what more precise localization of the lesions 

 were reported in rats (Hillarp, 1949). Con- 

 stant estrus was "consistently" produced by 

 bilateral, relatively large lesions placed im- 

 mediately anterior and ventral to the para- 

 ventricular nucleus, or by smaller, perfectly 

 bilateral, symmetrical lesions within the 

 area between the paraventricular nucleus 

 and the stalk. Lesions in the dorsal and 

 lateral hypothalamus did not affect the re- 

 productive functions. Eighteen other rats 

 with small lesions variously located in the 

 anterior hypothalamus showed cyclic irreg- 

 ularities and impaired reproductive capac- 

 ity with essentially normal appearing ova- 

 ries. Other more recent studies uniformly 

 emphasize the harmful effect of lesions in 

 the ventral hypothalamus and especially in 

 the median eminence on the reproductive 

 functions of the rat (IVIcCann, 1953; Bog- 

 danove and Halmi, 1953) ; man (Anderson, 

 Haymaker and Rappaport, 1950) ; cat 

 (Laqueur, McCann, Schreiner, Rosemberg, 

 Riocii and Anderson, 1955); sheep (Clegg, 

 Santolucito, Smith and Ganong, 1958). 



Although lesions in the median eminence 

 often produce some damage to the portal 

 circulation, the infrequency of infarction in 

 the anterior lobe and the usual retention of 

 normal morjihologic aspects of this gland 

 make it unlikely that the observed defi- 

 ciencies in gonadotrophic functions are as- 

 cribable to an inadequate vascular supply. 

 It is becoming increasingly evident that the 

 separate trophic functions of the anterior 

 lobe can be selectively altered by appropri- 

 ately placed lesions in the hypothalamus. 

 The relationship of hypothalamic lesions to 

 the thyrotrophic and adrenotrophic activi- 

 ties of the pituitary need not be considered 

 here, because these seem to be independent 

 mechanisms and exhibit no significant over- 

 lap with gonadal regulation. Evidence for 

 the selective effect of localized hypotha- 

 lamic lesions on pituitary trophic secretions 

 has been presented by Bogdanove and 

 Halmi (1953), Bogdanove, Spirtos and 

 Halmi (1955), Ganong, Fredrickson and 

 Hume (1955), and Bogdanove (1957). It 



