HYPOPHYSIS AND GONADOTROPHIC HORMONES 



trophins by the anterior hypophysis. Ob- 

 viously, central nervous pathways are in- 

 volved, but the anterior pituitary has so 

 little, if any, innervation that it is almost 

 certain that none of the impulses are carried 

 directly to the pituitary by this means. 

 An alternative connecting pathway between 

 brain and hypophysis exists in the form of 

 the portal vessels. One of the most pressing 

 problems in endocrinology is to define the 

 pathways and elucidate the mechanisms by 

 which such exteroceptive stimuli as those 

 mentioned above effect the secretory func- 

 tions of the anterior hypophysis. 



The hypothalamus serves in other re- 

 spects to receive impulses from higher affer- 

 ent centers and to instrument these into 

 responses that relate to vegetative func- 

 tions, for example, breathing, sleeping, and 

 body temperature. It is also known to be the 

 seat of neural mechanisms concerned with 

 sex functions. By location and neural con- 

 nections the hypothalamus could well be 

 attuned to the reception and integration of 

 sex-related impulses of variable sources. It 

 has often been observed clinically that tu- 

 mors of the hypothalamus are associated 

 v/ith disturbed sexual functions. Moreover, 

 anxiety states may lead to a cessation of 

 menstrual cycles or impotence without evi- 

 dence of organic disease. The supposition is 

 that chemotransmitters of some sort, arising 

 in the diencephalon, reach the pituitary 

 by way of the portal veins. Alternatively, 

 no other explanation of the existing evidence 

 is available. Such a chemotransmitter has 

 not yet been identified (Zuckerman, 1954). 

 Extracts of the hypothalamus have thus 

 far ])rovided only inconclusive evidence with 

 respect to release of another trophic factor, 

 corticotrophin, from the adenohypophysis 

 (Guillemin, Hearn, Cheek and Housiiolder, 

 1957). 



2. Electrical Stimulation of the Iljipothala- 

 mus 

 A hopeful means of increasing the secre- 

 tory activity of the anterior pituitary was 

 suggested by the observation that ovulation 

 and pscudoi)regnancy could be produced by 

 application of a strong current to the head 

 or spinal cord in estrous rabbits (Marshall 

 and Verney, 1936) and rats (Harris, 1936). 

 Witli refinement in the technique it has l)c- 



come possible to apply such stimulation to 

 precise areas in the pituitary and supra- 

 sellar region. Moreover, by use of implanted 

 electrodes and the remote induction of stim- 

 ulation it is possible to apply electric ex- 

 citation of controlled intensity to precise 

 areas for almost any length of time in un- 

 anesthetized animals (de Groot and Harris, 

 1950, reviewed by Harris, 1955). The 

 method has been used mainly in connection 

 with the study of ovulation in rabbits and 

 pseudopregnancy in rats, but the method 

 is suitable for much wider application in 

 the study of mechanisms which regulate the 

 functions of the pars distalis. By successive 

 steps an area wherein stimulation leads to 

 ovulation in estrous rabbits has been fairly 

 well delimited (Harris, 1937; Haterius and 

 Derbyshire, 1937; Markee, Sawyer and 

 Hollinshead, 1946; Harris, 1948b ).^ 



Stimulation of the various lobes of the 

 hypophysis and of the neurohypophyseal 

 stalk in the unanesthetized rabbit does not 

 promote ovulation, whereas ovulation is 

 quite regularly induced when the stimulat- 

 ing electrodes are in the tuber cinereum just 

 anterior to the median eminence or in areas 

 of the anterior hypothalamus. No part of 

 the supraoptic-hypophyseal tract yielded a 

 positive result. These observations provide 

 strong support for the belief that the hypo- 

 thalamus exerts a profound effect on the 

 reproductive functions of the pars distalis 

 and show finite conclusively that the con- 

 necting link to the pituitary is not neural 

 in character. They otherwise prove nothing 

 with respect to the essentiality of the portal 

 circulation in tlie mediation of these re- 

 sponses. 



Stimulation of the cervical sympathetic 

 fibers leading to the hypophysis neither in- 

 duces nor interferes with ovulation in rab- 

 l)its, according to Haterius (1934) and 

 Markee, Sawyer and Hollinshead (1946). 

 The few successful instances noted by Fried- 

 good and Pincus (1935) might have been 

 due to spread of the stimulus to the hypo- 

 thalamus, or a response to handling. It is 

 })ertinent to note in this connection that 

 neither sympathetic nor parasympathetic 

 denervation of the hypophysis has led to 

 any detectable change in pituitary func- 

 tions. 



