604 



Ontogeny of Endocrine Correlation 



ing growth processes shortly after birth mvist 

 be recognized, since (1) even prior to birth 

 the adrenal cortex becomes subnormal fol- 

 lowing hypophysectomy (decapitation) and 

 (2) in normal rats of 4 to 6 days post partum 

 the adrenal cortex is functionally responsive 

 to the administration of ACTH, as indicated 

 by hypertrophy (Moon, '40) and a decline 

 in ascorbic acid content (Jailer, '50). How- 

 ever, whether body growth can be modified 

 in opposite directions by administration of 

 growth hormone and ACTH or ACH to in- 

 fant rats remains to be analyzed. This early 

 period may be a critical one in which the 

 interlocking of hormonal function is still 

 undergoing progressive changes with age, 

 i.e., not yet fully integrated. This suggestion 

 is partly in keeping with the findings of 

 Jailer, who noted that (1) the administration 

 of adrenaline does not cause an increase in 

 ascorbic acid in the adrenal cortex until the 

 rat has attained an age of 8 days and (2) 

 upon exposure to low temperature (5°C.) 

 there is no decline in adrenal ascorbic acid 

 vmtil the sixteenth day after birth. It is of 

 interest in this connection to note in the 

 dwarf mouse that growth (increase in weight) 

 is as rapid as in unaffected sibs up until the 

 fourteenth day after birth (time of weaning), 

 after which time growth practically ceases, 

 dwarfism becoming manifest thereafter (see 

 pp. 586, 590 and 605). 



As to the time of onset of the growth- 

 promoting activity of the anterior pituitary 

 in the course of ontogeny in mammals, in- 

 formation of only a suggestive nature is 

 available (see Table 27). The preceding 

 analysis indicates that, as early as the sixth 

 day after birth of the rat, the anterior 

 pituitary seems to be essential for maintain- 

 ing a normal growth rate. In a similar man- 

 ner the thyroid is essential from the day of 

 birth. The question naturally arises next 

 as to the effects of removal of anterior pitui- 

 tary or thyroid from the fetus. Complete 

 removal of the pituitary by decapitation of 

 a 19- to 22-day fetal rabbit (Jost, '51a) or 

 by destruction by x-irradiation in a 13-day 

 fetal mouse (Raynaud and Frilley, '43, '47) 

 has yielded inadequate but nevertheless sug- 

 gestive results with respect to effects on 

 body growth. In the case of the rabbit fetus 

 general body development (similar in trunk 

 proportions, size, and fetal movements to 

 normal litter mates) seems to proceed in a 

 more or less normal manner in the absence of 

 the head until nearly term (28 days). Sim- 

 ilarly, body growth of a mouse fetus seems 

 to take place in a normal fashion when the 



thyroid is reduced to an epithelial nodule 

 (without follicles or colloid) by x-irradiation 

 of the buccal-pharyngeal region of a 13-day 

 embryo. These findings may be tentatively 

 interpreted as indicating that these glands 

 are not yet effective as regulators of body 

 growth during the late period in fetal life 

 of a mammal. In contrast to the mammalian 

 fetus, according to Fugo ('40) and Case ('52) 

 the chick embryo when hypophysectomized 

 (removal of all of the forebrain region) at 

 33 to 38 hours of incubation develops some- 

 what normally in body proportions and 

 shape, but the size of the body is consider- 

 ably smaller than in normal controls of the 

 same age (latter third of incubation). 

 Whether such contrasting effects can be 

 attributed to species differences or to a more 

 precocious onset of the growth-promoting ac- 

 tivity of the anterior pituitary in birds than 

 in mammals remains problematical. 



The hypothesis that the anterior pituitary 

 may be an ineffective regulator of body 

 growth of the mammalian fetus during the 

 later stages of development naturally raises 

 a number of questions. Dviring these stages 

 is growth-promoting activity absent? Or is 

 activity present without being released? If 

 unreleased, when is it first detectable, and 

 does it increase quantitatively with advance 

 in developmental age? So far as is known to 

 the writer, the only experiments designed to 

 answer some of these questions are those of 

 Smith and Dortzbach ('29). Using the hypo- 

 physectomized rat as a test animal, these 

 investigators found that daily implants of 

 the anterior pituitary from pig fetuses from 

 about 110 to 260 mm. elicit a definite body- 

 weight increase and skeletal growth of the 

 recipient. Moreover, the growth-promoting 

 effect appears to be specific, since implants 

 of other fetal tissues (muscle, brain, and 

 blood) fail to stimulate growth. Anterior 

 pituitary implants from smaller fetuses (70 

 to 90 mm.), even though the amount of 

 tissue used may be equivalent to that which 

 is effective from larger fetuses, do not pro- 

 duce a significant change in weight and 

 length. On the basis of the quantity of tissue 

 required it appears that, after activity is 

 first detectable, anterior pituitaries from suc- 

 cessively older pig fetuses become progres- 

 sively more effective in stimulating general 

 body growth of a juvenile rat dwarfed by 

 hypophysectomy. A gradual increase in 

 growth-promoting activity of the pituitary 

 with advance in fetal age is thus indicated. 



Is this initial appearance and increase in 

 growth-promoting activity of the anterior 



