504 



PHYSIOLOGY OF GONADS 



reaching the ghmd is greatly diminished, 

 through inactivation bj^ the liver (Biskind, 

 1941). 



Although it is true that estrogens have 

 a suppressing action on gonadotrophin se- 

 cretion, it has become increasingly evident 

 that they can also stimulate hypophyseal 

 function in certain ways, as Engle pro- 

 {)osed in 1931. Thus short-term injection of 

 estrogen into intact immature rats and mice 

 will invoke precocious puberty not only by 

 stimulating the sex accessories, but also by 

 increasing gonadotrophin secretion and thus 

 causing ovarian growth and even ovulation. 

 Frank, Kingery and Gustavson (1925j re- 

 ported that after such treatment regular 

 cycles continued after treatment was with- 

 drawn. Lane (1935) found that when 22- 

 day-old female rats were injected daily 

 with estrogen there was an early increase in 

 number of ovarian follicles, including vesic- 

 ular stages. After the first 10 days the non- 

 vesicular follicles became depressed al- 

 though vesicular follicles were retained. 

 This was interpreted to mean that for a 

 short time estrogen actually stimulates the 

 follicle-stimulating hormone (FSH) l)ut 

 eventually suppresses it, although lutein- 

 izing hormone (LH) secretion remains 

 elevated. Hohlweg (1934) had already dem- 

 onstrated that when somewhat older pre- 

 pubertal rats are given single, rather large 

 injections of estrogen, ovulation and corpus 

 luteum formation are induced within a few 

 days (p. 514). Obviously LH secretion is 

 greatly increased. 



Various bits of evidence implicate the 

 nervous system in the processes leading to 

 puberty and to the onset of estrus in sea- 

 sonal breeders. This will be discussed in the 

 following section with respect to the general 

 (juestion of the relationship of the hypo- 

 thalamus to gonadotrophin secretion. 



V. Follicular Cycles. Growth 

 and Atresia 



Attention will be focused here on the 

 dynamic pattern of follicle development 

 throughout the cycle, the extent to which 

 this i)attern depends on hyi)o[)hyseal con- 

 ti'ol, and the functional changes in the 

 o\aiy associated with estrus in preparation 

 foi' the more specialized events that lead to 

 ovuhition and corpus luteum formation. 



Production of primordial follicles and 

 the early growth stages have been said to 

 be independent of the hypophysis (Smith, 

 1939; Hisaw, 1947). This view derives from 

 the fact that following hypophysectomy the 

 ovaries retain large numbers of healthy 

 proliferating follicles below the stage of 

 antrum formation. There are, however, sev- 

 eral indications that these developmental 

 stages may be accelerated by gonadotrophic 

 stimulation. It was briefly reported by 

 Simpson and van Wagenen (1953) that ad- 

 ministration of purified FSH to immature 

 monkeys caused not only a 10- to 20-fold 

 'increase of ovarian weight, but also stimula- 

 tion of granulosa in follicles of all sizes. 

 Indirect evidence comes from the fact that 

 follicle atresia generally becomes maximal 

 late in estrus or metestrum, when depressed 

 FSH might be expected on theoretical 

 grounds. Harrison (1948) reported tliat in 

 ovaries of goats killed on the third or fourth 

 days of estrus healthy primary ovocytes are 

 rare. Some few, however, presumably re- 

 main. Myers, Young and Dempsey (1936) 

 stated that in the estrous guinea pig there 

 are few nonatretic follicles aside from those 

 destined for ovulation. However, small 

 numbers of normal ai)pearing nonvesicular 

 follicles were found. 



There seems to be general agreement that, 

 very quickly after this catastrophic elimi- 

 nation of follicles, renewed growth promptly 

 ensues. Whether or not the wave of atresia 

 represents a depression of FSH secretion, no 

 one would deny that tlie new growth reflects 

 this type of gonadotrophic stimulation. 

 Characteristically the population of small 

 and medium follicles is restored early in the 

 luteal phase of the polyestrous cycle. This 

 is clearly indicated for the guinea pig ovary 

 (Myers, Young and Dempsey, 1936) when 

 the data are converted from average vol- 

 umes to average diameters (Fig. 8.4). Be- 

 ginning on the fourth day after estrus, when 

 the largest follicles are approximately 300 fx 

 in diameter and when theca interna and 

 antra have formed, rapid growth of granu- 

 losa, theca, and antra continues for several 

 days. This is confirmed by counts of mitotic 

 figures obtained by the colchicine technique 

 (Schmidt, 1942), indicating greatest mitotic 

 activity in theca and granulosa of follicles 

 between 300 fi and 600 fx in diameter. By the 



