Ontogeny of Endocrine Correlation 



597 



hand, the activity of the male pituitary from 

 the time of birth rises gradually and con- 

 tinuously up to the age of puberty, attain- 

 ing at that time a high level which is more 

 or less uniformly maintained thereafter. 

 Similarly, in the rabbit the activity of ante- 

 rior pituitary tissue, as revealed by the rabbit 

 ovvilation test, is relatively low at 4 weeks 

 of age but at 3 months is as high as in adult 

 animals (Wolfe and Cleveland, '31). 



In sum, so far as the evidence for mammals 

 permits generalization, the gonadotropic 

 hormones apparently increase quantitatively 

 with advance in developmental age, begin- 

 ning during the later fetal stages, often 

 attaining a relatively high level at birth, 

 and usually the highest level prior to the 

 onset of sexual maturity. Possible exceptions 

 to this generalization may depend, even when 

 the unit dosage is constant, upon individual 

 and species variables in gonadotrophin con- 

 tent and in the degree of sensitivity of the 

 responding test organ of the recipient animal. 



A related problem for consideration is the 

 period in the course of development in which 

 the gonad, as a receptor gland, acquires the 

 capacity to respond to administered hypo- 

 physeal hormones. Is gonad responsivity 

 gradually or suddenly attained? In the classic 

 investigations of Smith ('27) and Smith and 

 Engle ('27) it was found that the number of 

 implants of anterior pitvxitary required to 

 induce precocious sexual maturity in male 

 and female rats and mice is higher in im- 

 mature than in older animals, the number 

 required being roughly inversely proportional 

 to the postnatal age of the host. Thus, in 

 general, as the recipients approach puberty 

 not only fewer implants but less time is 

 required to obtain the response. These ob- 

 servations clearly sviggest that the gonads 

 undergo developmental changes (maturation) 

 which enable them to respond gradually more 

 rapidly to hypophyseal stimulation. 



Subseqvient investigations have fully es- 

 tablished the concept of a gradual increase 

 in responsivity of the gonads after birth to 

 gonadotrophic stimulation. The time course 

 of development of gonad reactivity has been 

 particularly well worked out in the postnatal 

 rat by Price and Ortiz ('44). In the adminis- 

 tration of equine gonadotrophin particular 

 care was taken to keep the dosage and length 

 of treatment constant, the main significant 

 variable being the age of the recipient, which 

 ranged from the day of birth to maturity. The 

 degree of response at a given age was ascer- 

 tained by comparing with normal controls 

 the induced changes in weight and histology 



of the gonads and accessory reproductive 

 organs, the latter being end organs which 

 reflect changes in amount of sex hormones 

 liberated. Using these criteria, the ovary was 

 found to be only slightly responsive between 

 the day of birth and the sixth day of age; 

 between the fourth and tenth days a definite 

 though small response was indicated; and 

 at succeeding ages the response gradually 

 increased until a maximum was attained at 

 26 days of age. The response of the testis is 

 definite though relatively small between 

 birth and the sixth day. At successively later 

 ages the reactivity of the testis increases 

 rapidly and reaches a peak at 14 days. En- 

 hanced production of sex hormones by the 

 gonads is indicated by the response of at 

 least some of the accessory organs as early 

 as the sixth day in males and the tenth day 

 in females. In general, the capacity of the 

 gonads and accessory sex structures for 

 precocious structural differentiation develops 

 gradually in response to gonadotrophic stimu- 

 lation. Thus, in placental mammals (rat 

 and mouse) subsequent to birth a correlation 

 exists between the developmental age of the 

 gonads and their degree of responsivity to 

 gonadotrophins. 



Since within a few days after birth of the 

 rat the response is relatively weak, especially 

 in females, it might be expected that during 

 fetal stages the gonads would exhibit little 

 or no response to administered gonado- 

 trophin. Such appears to be the case, since 

 subcutaneous injection of equine gonado- 

 trophin into fetal rats near term fails, during 

 the short time interval allowed for action, to 

 bring about any significant increase in 

 growth of either the ovary or the testis; 

 however, the testis is otherwise stimulated 

 as is shown by a significant increase in the 

 size and number of the interstitial cells. No 

 increase in androgen secretion is indicated, 

 since enhanced development of the prostate 

 and other accessory sex structures is not 

 apparent (Wells, '46). 



The effects of treating young opossum in 

 the pouch at different ages (beginning on the 

 eighth day after birth) for short periods of 

 time with equine gonadotrophin reveals the 

 time at which the gonads are responsive to 

 the dosages used (Moore and Morgan, '43). 

 Capacity to respond occurs earlier in males 

 than in females. In males precocious develop- 

 ment of the prostate is readily produced sub- 

 sequent to but visually not earlier than the 

 seventieth day after birth. Since the response 

 of the prostate is a reliable indicator of 

 androgenic activity it is evident that the 



