Ontogeny of Endocrine Correlation 



605 



pituitary correlated in time with the cor- 

 responding development of thyroid activity? 

 In the fetal pig, insofar as the bio-assay 

 methods are reliable sensitive indicators of 

 activity, the thyroid hormone is first detect- 

 able by the metamorphosis test in anuran 

 tadpoles (see p. 583) in a fetus of 90 mm. in 

 length, which is approximately the stage 

 when growth-promoting activity of the an- 

 terior lobe is first detectable by the rat test. 

 Such a coincidence in the time of onset of 

 hormonal activity may not indicate a causal 

 connection, but merely the initial or pre- 

 paratory phases in the development of a 

 functional synergism between anterior pi- 

 tuitary and thyroid, a functional relationship 

 of established importance in regulating gen- 

 eral body growth of young mammals after 

 birth. Whether in the fetal pig the increase 

 in growth-promoting activity of the pituitary 

 is paralleled by increase in thyroid activity 

 is not known. Such an increase might be 

 expected, however, since in the bovine fetus 

 thyroid iodine increases quantitatively with 

 advance in fetal age. 



Since hypophysectomy of the mammalian 

 fetus disturbs the development of the adrenal 

 cortex, the gonad, and probably the thyroid, 

 presumptive evidence is furnished for the 

 view that specific trophic hormones con- 

 cerned with these receptor glands are re- 

 leased at least dviring the later stages of 

 fetal development. The apparent absence of 

 changes in over-all body growth of the fetus 

 after hypophysectomy, however, suggests 

 that specific growth-promoting activity is 

 not essential for the maintenance of fetal 

 body growth, a suggestion in keeping with 

 the observation on dwarf mice, where body 

 growth continues normally during fetal and 

 early postnatal life. The validity of these 

 suggestions may be tested by investigating 

 the effects of chemically purified hormones 

 either separately or in combination on the 

 normal fetus as well as on fetuses from 

 which one or more endocrine glands have 

 been removed. 



But few attempts have been made to 

 correlate the onset of growth-promoting ac- 

 tivity with the temporal course of differentia- 

 tion of the cell types of the anterior pitui- 

 tary (see Table 27). In the pig fetus the 

 stage (about 110 mm.) at which growth- 

 promoting activity is first detectable by the 

 rat test is preceded by a pronounced chro- 

 matophilic differentiation in which the 

 population of basophiles greatly exceeds that 

 of the acidophiles. In successively older 

 fetuses, however, the acidophile population 



gradually rises, becoming marked at 160- to 

 170-mm. stages. This rise seems to parallel 

 an apparent increase in growth-promoting 

 activity of the anterior lobe as noted above. It 

 is obviously difficult to assign to either type 

 of cell a functional role in the elaboration 

 of growth-promoting activity. It might be 

 suspected, however, that the acidophiles are 

 at least associated with the development of 

 such activity, since these cells form adenom- 

 atous tumors in such human disorders as 

 acromegaly and related gigantism (Sever- 

 inghaus, '36) and also since in the dwarf 

 mouse, according to Francis ('44), (a) the 

 number of typical acidophiles (accompanied 

 by an increase of chromophobes) becomes 

 markedly reduced at the time (twelfth day 

 after birth) when the young dwarfs can be 

 singled ovit from normal mice by length 

 measurement and weight, and (b) the typ- 

 ical acidophiles (only a few chromophobes 

 remain) are completely absent in the adult 

 dwarf. At corresponding ages in normal 

 mice (including those heterozygous for the 

 dwarf gene) the acidophiles and chromo- 

 phobes comprise the predominating types 

 of cell in the anterior lobe. The basophiles 

 are apparently not involved, since this type 

 of cell does not generally occur in the an- 

 terior lobe of normal mice at any age except 

 in those of advanced age or in pregnant 

 females. The problem of relating the func- 

 tional differentiation of cell types to the 

 prodviction of growth-promoting activity is 

 particularly complex, since, in addition to 

 the growth hormone, trophic hormones may 

 likewise be prodviced, the latter acting di- 

 rectly on such receptor glands as the thyroid 

 and adrenal cortex, stimulating them to 

 release secretions which play a role in regu- 

 lating the growth of an organism. 



By way of general interpretation, it may 

 be stated that during ontogeny there appears 

 to be a gradvial imfolding with time of 

 anterior pituitary and receptor-gland hor- 

 mones that act in harmony in regulating 

 the ultimate size and form of the body and 

 its component parts or organs. The functional 

 interlocking of these hormones, although 

 initiated in part during the later phases of 

 embryonic or fetal life, does not appear to 

 attain full expression vmtil postembryonic 

 stages of development. The period of elabora- 

 tion of growth-regulating hormones may be 

 regarded as a second phase in the develop- 

 mental realization of the specific constitu- 

 tional growth potential as provided by the 

 genotype of the fertilized egg. During this 

 phase, in contrast to an earlier one in which 



