The site and mechanism of action whereby barbiturates block the proestrous surge of LH and ovulation are unknown. The present study investigated the effects of pentobarbital (PB) on LH release in gonadectomized rats. Twenty—one days post—gonadectomy serial blood samples were withdrawn, via chronically implanted cannulae, at 30–min intervals from 0800–1100 or 1300–1600 hr. PB (30 mg/kg/ip) administration at 0830 hr significantly reduced the serum LH concentration of ovariectomized rats below the pre—drug control level at 0800 hr, and below the nearly constant level observed in saline injected controls between 0900 and 1030 hr. A significant rise in serum LH of ovariectomized rats occurred between 1400 and 1500 hr which was blocked by administration of PB at 1330–1345 hr. Castrated male rats did not show an afternoon rise in LH. PB lowered LH in males from 1400 to 1430 hr. The block of tonic LH release in males showed a shorter duration than in females, correlating with the shorter duration of anesthesia and the more rapid rate of disappearance of radioactivity from the serum after injection of 14C–PB in males. Our results indicate that: (1) PB reduces LH release independently of gonadal steroid action, and (2) a periodic neural timing center may exist for LH release in the ovariectomized female rat. (Endocrinology92: 1634, 1973)

Hypothalamic tyrosine hydroxylase (TH) activity of ovariectomized rats is modulated by gonadal steroids in vivo. The present study investigated the effects of ovariectomy and subsequent replacement of progestational and nonprogestational steroids on TH activity in vitro. All progestational steroids tested inhibited TH activity. Saturation of the A-ring of the steroid nucleus reduced apparent inhibitory activity. Kinetic studies revealed that both Vmax and Km were virtually unaltered for the substrate tyrosine in the presence of progesterone. Progesterone, in a dose dependent manner, increased the Km for the cofactor, DMPH4. These results suggest that progestational steroids decrease apparent TH activity by inhibiting the enzyme-reduced pteridine cofactor complex. (Endocrinology93: 1453, 1973)