Ontogeny of Endocrine Correlation 



603 



likewise found at successively earlier ages, 

 i.e., whether a gradual development of this 

 linkage takes place with increase in age. 

 In contrast to a somewhat abrupt cessation 

 of increase in body weight and length and 

 to a reduction in rate of skeletal growth in 

 rats deprived of the anterior pituitary at 28 

 days, rats hypophysectomized at 6 days of 

 age continue to gain in body weight and 

 length at a rate of about 50 per cent of nor- 

 mal for approximately three weeks, at which 

 time increase in weight ceases. Increase in 

 skeletal length and differentiation likewise 

 continues at a similar rate (60 per cent) for 

 the same period of time, whereupon it de- 

 clines abruptly to a still lower rate (20 per 

 cent), at which rate it continues for some 

 time (Walker et al., '50). Similar effects are 

 obtained by removal of the hypophysis from 

 rats at intermediate ages (13 and 21 days). 

 It would appear, therefore, that, irrespective 

 of the age of removal, the pituitaryless rat 

 continues to gain in body weight and length 

 and to advance in skeletal growth and differ- 

 entiation but only at a subnormal rate and 

 for a limited period. Eventually these proc- 

 esses are arrested. The time of arrest and 

 the developmental age ultimately attained 

 seem to vary in accord with the age of rat 

 at hypophysectomy. In general, the younger 

 the rat the greater is the amount of increase 

 in body weight and length subsequent to 

 hypophysectomy. 



At a glance these effects would seem to 

 indicate {a) a less complete regulation of 

 growth by the anterior pituitary in the rat 

 at earlier than at later ages subsequent to 

 birth and, as a corollary, {b) a rovigh index 

 of the amovmt of intrinsic growth capacity 

 that may be independent of the anterior 

 pituitary. However, such interpretations are 

 inadequate, since pituitary removal at early 

 ages disturbs the function of receptor endo- 

 crine glands, the secretions of which, as noted 

 above, likewise play a role in regulating 

 metabolic processes of growth. A functional 

 linkage with the thyroid at early postnatal 

 ages is indicated. Rats deprived of the thyroid 

 on the day of birth exhibit for a long period 

 (up to at least 111 days of age) an exceed- 

 ingly slow rate of increase in body weight 

 and length as well as in size of the skeleton. 

 Skeletal differentiation continues at a greatly 

 retarded rate. The administration of purified 

 growth hormone to such thyroidless rats (be- 

 ginning 30 days after thyroidectomy and 

 continviing for 30 days) increases body weight 

 (double that of untreated athyroid controls 

 of equivalent ages) and length; skeletal di- 



mensions increase, but skeletal differentiation 

 is no more advanced than in untreated thy- 

 roidless rats of equivalent ages. Other features 

 such as the ears, pelage, and genitalia re- 

 main immature. Thyroxine alone or in 

 combination with growth hormone stimulates 

 a marked increase in body weight (tripled 

 over that of untreated athyroid rats of the 

 same age) and in skeletal dimensions and 

 differentiation. The rate of gain in body 

 weight and skeletal dimensions appears to 

 be higher with thyroxine alone than with 

 growth hormone alone. Depending upon 

 dosage, thyroxine alone may accelerate dif- 

 ferentiation (skeleton) more than growth 

 increment. In combination with growth 

 hormone skeletal differentiation tends to 

 keep pace with growth increment (Ray et al., 

 '50). 



It is clear from the above considerations 

 that the growth processes in the postnatal 

 rat from the day of birth onward are greatly 

 altered by ablation of either the anterior 

 pituitary or the thyroid gland, indicating 

 that both glands are involved as essential 

 regulators. However, that normal growth 

 after birth is dependent upon secretions of 

 both glands is best brought out by treatment 

 of the thyroidless rat with thyroxine and 

 purified growth hormone, which in combina- 

 tion have a synergistic action in promoting 

 body growth. However, since the purified 

 hormones were not administered until the 

 athyroid rats had attained an age of 30 days 

 (i.e., after thyroid removal on the day of 

 birth), no indication is furnished as to 

 whether prior to this age these hormones 

 are equally effective in promoting or regulat- 

 ing growth, i.e., whether from the day of 

 birth onward an interlocking of function 

 exists or whether a certain degree of develop- 

 ment takes place before the rat is responsive 

 to the hormones. The fact that a significant 

 amount of growth takes place in the absence 

 of either gland poses problems relative to 

 the intrinsic growth potential (independent 

 of hormones) and the degree to which the 

 hormonal regulating mechanisms are es- 

 tablished at a given age. The solution to 

 these problems awaits further investigation. 



Whether ACTH, which as noted above 

 has a counteracting effect on the action of 

 the growth hormone on somatic growth of 

 older rats, likewise has a similar action on 

 normal rats or on those deprived of the 

 anterior lobe at early postnatal ages is a 

 problem as yet unresolved. The possibility 

 of a linkage of the hormones of the anterior 

 pituitary and the adrenal cortex in regulat- 



