1150 



SUBMAMMALIAN VERTEBRATES 



1947). Ovulation occurs 6 to 7 hours after 

 intravenous LH injection (Fraps, Riley and 

 Olsen, 1942). After intravenous progesterone 

 injection which induces gonadotrophin re- 

 lease from the pituitary, ovulation occurs 

 in 7 to 8 hours (Fraps, 1955b). The ques- 

 tion of how long the pituitary would have 

 to remain active in order to secrete enough 

 gonadotrophin for ovulation was investi- 

 gated by Rothchild and Fraps ( 1949a j. 

 Hypophysectomy was performed at various 

 intervals before "spontaneous" ovulation. 

 The results showed that ovulation would 

 still occur in 60 per cent of the cases when 

 the interval was 5 hours, but only 20 per 

 cent would ovulate when the interval was 

 7.2 hours. Progesterone-induced ovulation 

 provided, of course, a better estimate how 

 long it takes to secrete sufficient gonado- 

 trophin because the time of stimulation of 

 the pituitary can be timed better. As the 

 intervals between LH or progesterone in- 

 jection and ovulation agreed rather closely, 

 it was assumed that the stimulation for 

 gonadotrophin secretion after progesterone 

 was immediate. Rothchild and Fraps 

 (1949b I established that the pituitary has 

 to remain in situ 2 to 4 hours after the in- 

 jection of progesterone in order to obtain 

 ovulation. The question as to the duration 

 of stimulation of the pituitary was investi- 

 gated by "blocking" the stimulus with 

 atropine (van Tienhoven, 1955), and by 

 destroying the hypothalamic centers (Ralph 

 and Fraps, 1959) at various time intervals 

 after progesterone injection. In van Tien- 

 hoven 's experiments the estimate was that 

 26 minutes was the minimum and about 2.5 

 hours the maximum, whereas Ralph and 

 Fraps found that the lesion had to be made 

 within 2 hours after the injection. 



In a typical closed cycle which has been 

 discussed so far, the Ci follicle is ovulated 

 about 6:00 a.m. on day 1 and laid the next 

 day about 8:00 a.m. The C2 follicle ovulates 

 about 8:30 a.m. of day 2 and is laid about 

 10:00 a.m. of day 3. The C„ follicle is 

 ovulated about noon and laid in the after- 

 noon of the nth + 1 day of the cycle. On 

 this day no ovulation occurs in spite of: 

 (1) greater sensitivity of the C'l follicle 

 (first follicle in the second clutch) at this 

 time to LH than any subsequent follicles 



of the same clutch (Fraps, 1946; Bastian and 

 Zarrow, 1953); and (2) competence of the 

 ])ituitary to secrete ovulation-inducing 

 amounts of gonadotrophin when stimulated 

 by progesterone. Neher and Fraps (1950> 

 were, for example, able to add as many as 

 13 eggs to the clutch by injecting proges- 

 terone at times calculated to stimulate ovu- 

 lation at a time corresponding to the nth + 

 1 follicle of the clutch. In this manner, the 

 C'l follicle became the /^th + 1 follicle of 

 the first clutch. By injecting progesterone 

 from then on at 26-hour intervals more eggs 

 were added to the clutch. Thus, the situa- 

 tion is, in a typical closed cycle, that ovula- 

 tion fails to occur in spite of the presence of 

 an ovulable follicle and in spite of the abil- 

 ity of the pituitary to secrete enough gon- 

 adotrophin. 



Various hyi)otheses have been proposed to 

 exjilain this jihenomenon. Bastian and Zar- 

 row (1953) and Fraps (1955b) agree that 

 light and activity are the regulatory mecha- 

 nisms which impose the rhythm of ovula- 

 tions. Bastian and Zarrow (1953) proposed 

 that two independent rhythms, a 24-hour 

 daily rhythm and rhythmic maturation of 

 follicles, interact to produce an asynchro- 

 nous ovulation cycle. The inference would 

 l)e, if this is true, that succeeding follicles 

 in a clutch would be more and more imma- 

 ture as the ovulations of the clutch pro- 

 gressed. Some evidence was obtained to show 

 that this occurred: the yolks of the second 

 and third eggs of 2- and 3-egg clutches were 

 indeed smaller than the yolk of the first egg 

 of the clutch (Bastian and Zarrow, 1953) ; 

 furthermore, the follicles became less and 

 less sensitive to LH. As stated above, the 

 first follicle of a clutch is more sensitive to 

 LH than the succeeding ones. Thus, the fail- 

 ure of the C/ follicle to ovulate as the nth + 

 1 follicle would be due to its low sensitivity 

 to LH. This is not in agreement with Fraps' 

 data (1955b) showing that the sensitivity to 

 gonadotrophins for the follicles of a clutch 

 is about the same at the same time interval 

 after the preceding ovulation. Thus, the fol- 

 licle is equally sensitive to LH at the same 

 interval after previous ovulation as all folli- 

 cles of the clutch are after that interval. In- 

 asmuch as no ovulation occurs, sensitivity of 

 the Ci follicle increases, so that at the same 



