600 



Ontogeny of Endocrine Correlation 



true, what regulates the gradual release? 

 Answers to these questions await further in- 

 vestigation. 



ANTERIOR PITUITARY AND GROWTH 



In addition to the production of specific 

 trophic hormones which act selectively on 

 the growth and function of certain "target" 

 endocrine glands, the anterior pituitary pro- 

 duces a growth hormone which plays an 

 essential role in governing the general body 

 growth of the organism. The concept had its 

 origin from observations on human dis- 

 orders, gigantism and acromegaly, in which 

 overgrowth of the body or its parts is a 

 characteristic feature. Since the overgrowth 

 was usually associated with an adenomatous 

 enlargement of the anterior lobe, the condi- 

 tion was attributed to an overabundance of 

 some growth-promoting principle. Conversely, 

 it gradually became apparent that certain 

 types of arrested growth, i.e., pituitary 

 dwarfism, might be associated with an 

 underactivity of the anterior lobe. Such pre- 

 sumptive evidence initiated, over 40 years 

 ago (1912), an era of experimentation which 

 has continued up to the present time. 



Three high lights in the history of the 

 concept may be recognized. (1) The ante- 

 rior pituitary is essential for growth, since 

 (a) complete hypophysectomy of an im- 

 mature animal arrests growth and results in 

 dwarfism, and {b) implants and crude ex- 

 tracts can restore growth in hypophysecto- 

 mized animals and augment growth in 

 normal animals (first clearly established in 

 the rat by Smith, '30). (2) Experimental 

 dwarfism is insufficient proof for the view 

 that a specific hormone exclusively concerned 

 with growth is secreted, since removal of the 

 anterior lobe likewise causes growth regres- 

 sion and diminished function of the gonad, 

 thyroid, and adrenal cortex, secretions of 

 the last two being clearly essential for nor- 

 mal growth. Cessation of growth after hypo- 

 physectomy thus appeared to be partly, at 

 least, the result of multiple gland deficiency. 

 As a consequence the principle came to be 

 recognized that the hypophyseal hormones, 

 through an interplay with other hormones 

 and nutritional factors as well as genetic 

 constitution, determine the ultimate size and 

 form of the body and its component organs or 

 parts. (3) Isolation of the growth hormone in 

 chemically pui-ified form by Li, Evans, and 

 Simpson ('45). 



In broad terms the objective here is, so far 

 as the data permit, to trace during the course 



of ontogeny the succession of events in the 

 establishment of the functions of the ante- 

 rior pituitary as related to the over-all growth 

 of the body. Attention will be centered on 

 such problems as (a) the time and degree to 

 which the anterior pituitary is essential to 

 the promotion of bodily growth, {b) the 

 interplay of hypophyseal growth hormones 

 and hormones of "target" glands in main- 

 taining the metabolic processes of organismic 

 growth, and (c) concomitant dependence up- 

 on the genotypic constitution, nutritional 

 factors, etc. of the organism. 



That the growth of the body in the anuran 

 tadpole is dependent vipon growth-promoting 

 substances of the anterior pituitary is clearly 

 indicated (see Table 27). Ablation of the 

 ingrowing primordium of the anterior lobe 

 from the early anuran embryo results in a 

 diminished growth rate of the body as a 

 whole. At first growth retardation is scarcely 

 noticeable, but at about the mid-larval period 

 (30 to 32 mm.) it is pronounced, at which 

 time "an abrupt change in the direction of 

 the growth curve ensues" (Smith, '20, p. 46). 

 This marked drop in velocity of growth, 

 designated as the "critical point," is followed 

 by a later period of continuous but slow rate 

 of growth. Moreover, the fat-body becomes 

 unusually large, indicating that the utiliza- 

 tion of fat is disturbed and contrasting 

 sharply with the minute size of the fat-body 

 of the normal tadpole at the time of com- 

 pletion of metamorphosis. Growth in size 

 of the hypophysectomized tadpole is restored 

 essentially to normal in three ways: by feed- 

 ing fresh anterior lobe (bovine) or dried 

 residues thereof (Smith, '18, '20), by trans- 

 plantation of anterior lobe from adult frogs 

 (Allen, '28), and by intraperitoneal injection 

 of extracts of bovine pars anterior (Smith and 

 Smith, '23). By the latter treatment the 

 volume of the hypophysectomized tadpole in 

 a period of three months may be increased to 

 three times that of uninjected normal con- 

 trols, and the growth of normal tadpoles 

 may be accelerated by an increase of twice 

 the volume of uninjected normal controls. 

 The ultimate attainment of a size notably in 

 excess of the normal in the treated hypo- 

 physectomized tadpoles may be attributed in 

 part to the persistence of the larval period 

 and consequent extension of the larval 

 growth span (Smith, '20). 



Although the hypophysis is undoubtedly 

 essential to the growth of the tadpole, it is 

 by no means certain that a single growth- 

 promoting principle is concerned. The situa- 

 tion is complicated by the fact that cessation 



