Dose Dependent Effects of Progesterone on the Facilitation and Inhibition of Spontaneous Gonadotropin Surges in Estrogen Treated Ovariectomized Rats

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Abstract
These studies determined whether fluctuating physiological plasma progesterone (P) concentrations facilitate as well as inhibit spontaneous LH [lutropin] and FSH [follitropin] surges in E2 [estradiol] primed, ovariectomized (OVX) rats. Two weeks after ovariectomy (day 0), Silastic implants of E2 were inserted s.c. at 0900 h into all animals. Silastic P implants of various lengths, which produced plasma P levels ranging between 5-20 ng/ml, were implanted s.c. into separate groups of E2 treated OVX rats 72 h later (day 3). Another group of E2 treated rats received a s.c. injection of 2 mg P on day 3. As plasma P levels increased, greater peak plasma LH and FSH levels were achieved during the afternoon of day 3. However, higher concentrations of plasma P were required to affect significantly spontaneous FSH than LH surges. Further, as plasma levels of P increased, the onset of release of both gonadotropins occurred earlier in the afternoon of day 3. When plasma P levels were increased above 17 ng/ml, further facilitation of either gonadotropin surge was not observed. Regardless of the plasma P levels present on day 3, this steroid did not inhibit spontaneous LH surges on this day. In contrast, the absence of spontaneous gonadotropin surges on day 4 was related to P concentrations present in plasma on days 3 and 4. In a separate experiment, the pituitary LH responses to 2 i.v. pulse injections of LHRH [luliberin] spaced 120 min apart were evaluated in 2 wk OVX animals given E2, E2P or no steroid pretreatment. Both steroid treated groups released more LH than did nonsteroid treated animals in response to either LHRH injection. As well, pituitary LH responses to LHRH in E2 and E2 P treated rats were greater after the 2nd than after the 1st injection. However, P treatment of E2 primed animals tended to enhance the self-priming action of LHRH. Low physiological P levels can facilitate spontaneous LH and FSH surges on day 3 as well as inhibit these discharges on day 4 in E2 primed animals. These P-induced responses are dose dependent. The facilitory action of P is exerted on CNS neurons and possibly on pituitary gonadotrophs.

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