512 



PHYSIOLOGY OF GONADS 



eral hypophyses in which there was pro- 

 nounced central necrosis in company with 

 well regenerated portal vessels. A study by 

 Nikitovitch-Winer and Everett (1957, 

 1958b) established beyond doubt that quali- 

 tative functional losses after stalk-sectron 

 or transplantation of the pars distalis result, 

 not from impaired blood supply per se, but 

 from the loss of the intimate neurovascular 

 relationship with the hypothalamus. Hy- 

 po])hyseal autografts, after first being 

 placed under the kidney capsule for sev- 

 eral weeks with the usual atrophy of the 

 ovarian follicular apparatus and interstitial 

 tissue, were later retransplanted to a site 

 immediately under the median eminence. In 

 the definitive series of 14 such experiments, 

 13 rats resumed estrous cycles spontane- 

 ously 8 to 68 days after retransplantation ; 

 7 were fertile and carried litters to term. A 

 correlated study (Nikitovitch-Winer and 

 Everett, 1959) demonstrated clearly that on 

 the occasion of each of these successive 

 transplantations there was massive necrosis 

 of the interior of the glandular mass, leav- 

 ing but a thin shell from which the func- 

 tional tissue of the graft was reconstituted. 

 In spite of this double insult some special 

 influence of the hypothalamus brought 

 about renewed function in a surprising num- 

 ber of cases. Together with the restoration 

 of gonadotrophic activity there was signifi- 

 cant improvement in thyroid-stimulating 

 hormone (TSH) and adrenocorticotrophic 

 hormone (ACTH) secretion. The consider- 

 able net loss of hypophyseal parenchyma 

 resulting from the two operations was re- 

 flected only quantitatively in the effects on 

 the various target organs. Ovarian weights, 

 numbers of follicles and corpora lutea, ad- 

 renal weights and extent of adrenal hyper- 

 troi)liy after unilateral adrenalectomy, and 

 thyroid uptake of P^^ were all intermediate 

 between those of the normal female rat and 

 control animals in which the graft remained 

 on the kidney or was retransplanted under 

 the temporal lobe of the brain. 



Regulation of pars distalis secretion by 

 means of the stalk vessels may conceivably 

 be carried out either by regulation of blood 

 How or by transmission of chemical media- 

 toi-s from the proximal capillary plexus in 

 the median eminence to the pars distalis. An 



experiment describetl by Swingle, Seay, 

 Perlmutt, Collins, Fedor and Barlow (1951) 

 suggested that a mediator subject to Diben- 

 amine blockade might be involved in pre- 

 cocious puberty. Although significant uter- 

 ine enlargement was produced in immature 

 rats by daily stimulation of the cervix uteri 

 for 10 days, no such effects were observed 

 in similar rats given Dibenamine daily by 

 stomach tube. Unfortunately, there were no 

 controls for the possible effect of Diben- 

 amine in nonstimulated or gonadotrophin- 

 injected animals. 



Fluhmann (1952) invoked precocious 

 vaginal opening and ovarian stimulation in 

 immature rats by injection of neostigmine. 

 The locus of such cholinergic action is un- 

 known. Parenthetically, Barbarossa and di 

 Ferrante (1950) reported follicle stimula- 

 tion in immature rats after injection of 

 intermedin, an effect not found in hypophy- 

 sectomized subjects. Benoit and Assen- 

 macher (1955) proposed that, in the drake, 

 gonad-stimulating activity is governed by 

 an agent contained in neurosecretory sub- 

 stance, which is demonstrable in abundance 

 in the retrochiasmatic region of the median 

 eminence. Capillaries there drain selectively 

 into an anterior set of portal venules. Oxy- 

 tocin has been suggested as a possible medi- 

 ator for gonadotrophin secretion (Shibu- 

 sawa, Saito, Fukuda, Kawai, Yamada 

 and Tomizawa, 1955; Armstrong and 

 Hansel, 1958). There is much interest 

 as this is being written (1958) in the 

 jiossibility that vasopressin, oxytocin, or 

 other agents associated with neurosecre- 

 tory substances of the neui-ohyjioiihysis 

 are responsible for control of produc- 

 tion and release of the various trophic 

 hormones of the pars distalis. As an 

 alternative or even a supplement to neu- 

 rochemical regulation, a vasomotor mecha- 

 nism cannot be denied (Green, 1951), for 

 conceivably only a slight shift in blood flow 

 through the jiars distalis might tip the bal- 

 ance of hormone production one way oi- an- 

 othei-. Thus the matter stands: whereas it 

 is apjiarent that the hypothalamus inter- 

 venes in follicle growth and estrogen secre- 

 tion, how it does so is little more than spec- 

 ulati\'e. 



