598 



Ontogeny of Endocrine Correlation 



pi'oduction and release of male sex hormones 

 by the testis are enhanced by gonadotrophin. 

 In older treated males interstitial cell hyper- 

 trophy occurs but spermatogenesis is not 

 hastened. Using the marked response of the 

 uterus as a sign of increased liberation of 

 estrogens by the ovary, there is no apparent 

 stimulation of the ovary by gonadotrophin 

 prior to the hundredth day after birth. How- 

 ever, at the age of 125 days the ovary is def- 

 initely stimulated in follicular development 

 and in luteinization and, as is signalized by 

 the accelerated development of the uterus, 

 in the production and release of ovarian 

 hormone. 



The gonad of the chick likewise shows an 

 increase in capacity to respond to gonado- 

 trophic hormones with advance in develop- 

 mental age. According to Domm ('37), in 

 chick embryos examined at 18 days following 

 daily injections of pituitary extracts ("He- 

 bin"), beginning at a time just prior to and 

 continuing throvigh the period of morpho- 

 logical sex differentiation (5 to 9 days of 

 incubation), the gonads in both sexes are 

 hypertrophied, apparently as a result of a 

 marked increase in intertubular tissue of the 

 testis and of medvillary tissue in right and 

 left ovaries. There is, however, no significant 

 advance in the differentiation of either the 

 seminiferous cords or the ovarian cortex. 

 Although structural changes are produced, 

 little or no enhancement of sex-hormone 

 activity is indicated, since neither the comb 

 nor the gonoducts in either sex show any 

 significant change from the normal. 



The responsiveness of the gonads in newly 

 hatched chicks to daily pituitary injections 

 is still further increased with certain striking 

 sex differences. In contrast to the embryo, 

 a precocious spermatogenesis sets in and sex 

 hormone is actively released by the testis, as 

 is indicated by a precocious onset of male 

 sex behavior, an accelerated growth of the 

 head furnishings, and a hypertrophy of the 

 ductus deferens. In the female, although no 

 increased follicle growth in the ovarian cor- 

 tex is apparent, the oviduct is hypertrophied, 

 an indication of enhanced production of 

 female sex hormone. Curiously, whereas the 

 right ovary is unmodified, the medulla of the 

 left ovary shows a pronounced hypertrophy. 

 Since medullary hypertrophy is regularly 

 associated with an accelerated growth and 

 masculinization of the head furnishings, it 

 may be assumed that the left ovarian me- 

 dulla is the source of male hormone xm.der 

 the conditions of the experiment. 



Although the time of initial response to 



administei^ed gonadotrophins has not been 

 ascertained, it is clearly evident from the 

 above data that the gonads, which are al- 

 ready highly reactive by the eighteenth day 

 of incubation, become still more so in 

 newly hatched chicks and probably reach 

 a maximum in still older chicks. Apparently, 

 then, as the gonads undergo developmental 

 changes, their reactivity to hypophyseal 

 stimulation progressively increases. 



In the salamander (Amblystoma tigrinum) 

 the time sequence in the development of 

 gonad reactivity has been worked out fairly 

 completely by Burns ('34) and Burns and 

 Buyse ('31, '33, '34). The administration of 

 hypophyseal substances to young larvae (30 

 to 35 mm. long) at the stage of sex differen- 

 tiation readily stimulates precocious growth 

 and maturation. Gametogenesis sets in pre- 

 cociously in both sexes but to a much greater 

 degree in males than in females, indicating 

 a sex difference in time of attainment of the 

 responsive state. However, soon after meta- 

 morphosis at a time when the gonads are 

 still very immature (sexual maturity in the 

 normal is attained many months later), the 

 growth of the testis and of the ovary as well 

 is greatly enhanced by hypophyseal extracts. 

 In males spermatogenesis reaches a peak in- 

 cluding the formation of mature spermatozoa; 

 in females many of the ova are practically 

 mature, although falling short of nuclear 

 maturation and ovulation. It is thus apparent 

 that the gonads of post-metamorphic stages 

 have acquired a marked capacity for pre- 

 cocious growth stimulation in sharp contrast 

 to a much more limited yet definite capacity 

 for induced growth during the larval period. 



The question next arises as to whether the 

 progressive increase in gonad reactivity is 

 dependent upon the liberation of gonado- 

 trophic hormones during the course of nor- 

 mal development. As many studies show 

 (for backgroxuid evidence and citations see 

 Smith, '39), in sexually immature stages 

 (from a few days after birth to onset of 

 sexual maturity) of mammals (rat and 

 mouse), ablation of the anterior lobe dvu-ing 

 the period when the gonad is shown to be 

 responsive to administered gonadotrophin 

 results in either arrested development or a 

 retrogression of the gonad to a more im- 

 mature state. Structural maturation of the 

 gonad is arrested and functional activity 

 ceases, as is reflected in the atrophic state 

 of sex-hormone dependent structures such as 

 the uterus, prostate, and seminal vesicle. 

 Generally speaking, the extent of retrogressive 

 change appears to be roughly proportional 



