CENTRAL CONTROL OF PITUITARY SECRETION 



IOI3 



within 30 sec. of copulation (297). Similarly in rats, 

 the spontaneous ovulation in this form could be 

 blocked by Dibcnamine or atropine (95J, and by 

 pentobarbital and other barbiturates (94). Ovulation 

 is delayed by 24 to 76 hr. in the cow after atropine 

 administration (146). Estrogens stimulate the release 

 of LH in the rat and if administered to the pregnant 

 animal will result in ovulation. This response may be 

 blocked in a high proportion of cases by Dibenamine 

 or atropine injected prior to, or as much as 20 hr. 

 after, estrogen administration (294). In another form, 

 the hen, ovulation is induced by progesterone (iio). 

 This action of progesterone may also be blocked by 

 Dibcnamine (336). The site of action of such drugs as 

 atropine, Dibenamine and SKF-501 in blocking ovu- 

 lation is not clearly established. Markee and his 

 co-workers put forward the suggestion that atropine 

 acts, in this respect, i)y blocking synaptic transmission 

 in the hypothalamus and that sympatholytic drugs 

 act by blocking an adrenergic mechanism at the por- 

 tal vessel-pituitary level. The results obtained by the 

 use of such drugs do not point solely in the direction 

 of an adrenergic agent as being the humoral trans- 

 mitter since Dibenamine possesses some antihista- 

 minic activity (249) and is said to be a powerful 

 antagonist of 5-hydroxytryptamine (91). 



Benoit & Assenmacher {23, 32) have produced 

 evidence that a stainable neurosecretory material, 

 originating perhaps in the tuberal nuclei, may play 

 a role in the regulation of gonadotrophic secretion. 



HUMORAL STIMULATION OF ACTH, TSH AND LACTOGENIC 



SECRETION. The most direct data regarding humoral 

 control of ACTH secretion are those reported by 

 Porter & Jones (268). These workers hypophysecto- 

 mized dogs and collected blood from the empty sella 

 turcica, blood that was derived in part from the 

 upper cut end of the pituitary stalk. The ACTH- 

 releasing potency of this blood was studied by injec- 

 tion into rats pretreated with hydrocortisone. (Such 

 animals were found not to respond to the stress of 

 unilateral adrenalectomy with adrenal ascorbic acid 

 depletion.) Injection of portal vessel blood caused 

 adrenal ascorbic acid depletion in hydrocortisone- 

 inhibited rats but not in hypophysectomized rats, 

 while injection of blood obtained from the carotid 

 artery of the dog did not cause ascorbic acid depletion 

 in either the hydrocortisone-treated or hypophy- 

 sectoinized animal. The conclusion is drawn that 

 some substance is present in blood drawn from the 

 hypophysial portal vessels, but not in carotid artery 

 blood, that evokes ACTH release from the anterior 



pituitary by a direct action on the gland. Somewhat 

 similar results have been obtained by Schapiro el al. 

 (302) who collected blood from the jugular vein of 

 stressed hypophysectomized rats and showed this 

 blood was active in eliciting ACTH release in rats 

 in which a hypothalamic lesion had been placed 

 that blocked a stress response. Porter & Rumsfeld 

 (269) have fractionated portal vessel plasma, and 

 their results indicate that the substance responsible 

 for pituitary activation is either a large protein 

 molecule or is bound to a large protein molecule and 

 is probably not vasopressin. 



Some years ago Long and his collaborators sug- 

 gested that medullary hormones .secreted \>\ the 

 adrenal gland might play a part in the stimulation of 

 ACTH release following stressful stimuli. While the 

 medullary hormones may play a role in stress activa- 

 tion of the adrenal corte.x in the normal animal, they 

 cannot be regarded as essential to the response since 

 adrenal demedullation has been found by many 

 workers (see 159) not to affect the adrenocortico- 

 trophic effect of stress. However, the above data and 

 the fact that epinephrine has been shown to exert a 

 direct effect on transplanted anterior pituitary ti.ssue 

 (!o6, 237) raised the possibility of an adrenergic 

 mechanism underlying hypothalamic activation of 

 ACTH release via the portal vessels. Evidence on this 

 point has been obtained with the use of sympatholytic 

 agents. Some of the early investigators reported a 

 partial blockade of the ACTH response to stress by 

 ergotamine (285), Dibenamine (257, 285, 308) and 

 N - (g - fluorenyl) - N - ethyl - fi - chloroethylamine 

 hydrochloride (SKF-50!) (29BJ, while in the hands 

 of other workers Dibenamine (104, 326), ergotamine 

 (121) and dihydroergocornin (11) proved ineffective 

 in modifying the stress response. One complication 

 encountered in these studies was the fact that admin- 

 istration of the blockading drug is in itself a nonspecific 

 stress and evokes ACTH discharge. This difficulty has 

 since been overcome by inducing a state of adaptation 

 to the blockading drug by repeated administrations 

 prior to the experiment. Using this technique, Guil- 

 lemin (136) has shown that treatment of rats with 

 SKF-501 and dibenzyline blocks the release of ACTH 

 consequent to administration of epinephrine or nor- 

 epinephrine while the adrenal a.scorbic acid response 

 to the stress of formalin administration or immo- 

 bilization is unaltered. These, and similar experiments 

 using Phenergan (138) and atropine (136), militate 

 strongly against the necessary participation of a 

 cholinergic, adrenergic or histaminergic link in hy- 

 pothalamopituitary activation. One pharmacological 



