36 Discussion 



doing, through the next stage, which is that of cell division. In this case, of course, 

 this is the reduction division. 



Then there came the necessity of restricting the season of reproduction. Food is 

 plentiful in autumn, but it is a poor time for young animals to have to start their 

 development. I suppose this seasonal restriction was imposed, first of all, by the 

 granulosa cells, inhibiting the germinal meiosis, and secondly, that the granulosa came 

 under the influence of the pituitary through the regulation of the thecal-organizing 

 substance. 



I imagine that the first gonadotropin was something like PMS, with both FSH and 

 LH activities, and that the response of the thecal cell depended on its maturity. I here 

 partly follow, with modification, the ideas of Gadrenstroom and de Jongh (Research 

 in Holland. Elsevier, Amsterdam, 1946). When the thecal cell was young it responded 

 to the FSH part of the molecule, and the FSH caused thecal estrogen secretion which 

 maintained the granulosa cells. As the thecal cell became older it responded to the 

 LH part of the molecule, and secreted androgen that produced the effect of destroying 

 the granulosa, thus removing the inhibition to meiosis and at the same time freeing 

 the egg. 



When estrogen becomes a hormone as well as an organizer, its output has to increase 

 as the follicle ripens — when one supposes the theca becomes reactive to LH. One may 

 imagine, then, the evolution of LH as a separate hormone, synergizing with FSH for 

 estrogen secretion; and also the evolution of interstitial cells, derived from the theca 

 and stimulated by LH, in which estrogen can be produced at a site remote from the 

 follicle — and so can act as a hormone without also having an effect on the follicle 

 where it might antagonize the presumed thecal androgen production, which organizes 

 ovulation by destroying the granulosa. Later still, the granulosa will not be destroyed, 

 but stimulated to luteinize when vascularized. 



Finally, a question I would like to put to Dr. Noyes. How do you know that the 

 follicles haven't been stimulated and maturation changes initiated by discharge from 

 the host pituitary before you give chorionic gonadotropin? 



