146 Rk HARD M. FRAPS 



explanation may be based on the supposition tliat these barbiturates suppress 

 activity in a region or "center" which inhibits, during the period of lapse, 

 another hypothalamic "center" directly responsible for neurohumoral activa- 

 tion of the pituitary. Such a view is in accord with the observation that release 

 of 01 H for C, ovulation is most closely associated with onset of darkness 

 (according to our calculations), and that light plus activity act to suppress 

 OIH release (3). The discovery of the "stimulatory" effects of lesions by 

 Donovan and van der Werff ten Bosch (8, 9), discussed elsewhere in these 

 proceedings (p. 56), may afford grounds for speculation on the operation of 

 such mechanisms on a diurnal scale. 



Phcnobarbital sodium, injected under the same conditions as were 

 Nembutal, Dial and Ipral calcium, failed either to induce ovulation prema- 

 turely or to block ovulation of the Cj follicle (19). The drug was found how- 

 ever to prevent some 40-50% of expected ovulations of Q follicles (Fraps 

 and Conner, cited in (17)). Phcnobarbital sodium also effectively blocks the 

 ovulation-inducing action of progesterone and other steroids on the Ci follicle 

 when administered 30-40 min before injection of the steroids (17). 



The action of other pharmacological agents has also been investigated in 

 the hen. Zarrow and Bastian (70) reported blockade of both normally 

 expected and progesterone-induced ovulation of the Cj follicle by the para- 

 sympatholytic drug, atropine and the adrenolytic agent, SKF-501. Dibena- 

 mine (A'^,A^-dibenzyl-B-chloroethylamine), presumably an adrenergic blocking 

 agent, was shown by van Tienhoven, Nalbandov and Norton (66) likewise 

 to block both normal and progesterone-induced ovulation. The drug was 

 increasingly effective in preventing normal ovulation as the interval between 

 injection and expected ovulation was increased from 6 to 14 hr, with the 

 notable exception of an unaccountably low incidence of blocked ovulations 

 at 12 hr. Their observations led van Tienhoven et al. to suggest that "the 

 stimulus for LH release and hence ovulation takes place about 14 hours 

 prior to follicle rupture", an interval considerably greater than that favored 

 by this author — some 8 hr — on other grounds. 



The increasing effectiveness of presumptive blocking agents with increasing 

 interval from injection of submaximal levels to expected ovulation has been 

 observed often in our laboratory. When administered 38 hr before expected 

 ovulation of the Cj follicle, Dial, Nembutal, phcnobarbital sodium, Dibena- 

 mine, SKF-501 and atropine sulfate all effectively suppress ovulation (20), a 

 result which may possibly stem from interruption of mechanisms other than 

 those responsible for OIH release. 



In a subsequent study, van Tienhoven (64) attempted to determine the 

 duration of stimulation of the hen's anterior pituitary for progesterone- 

 induced OIH release, using atropine and Dibenamine to block the release. 

 He noted a longer duration of stimulation from the adrenergic than from the 

 cholinergic component; for the adrenergic component the duration of 



