Estrogen-primed Ovariectomized Rats Research Articles

Effect of progesterone and its 5 alpha-reduced metabolites on gonadotropin levels in estrogen-primed ovariectomized rats.

In an effort to determine whether the metabolic conversion of progestrone may be important in the feedback effects of this steroid, serum LH and FSH levels were measured after administration of progesterone, 5 alpha-dihydroprogesterone or 3 alpha-hydroxy-5 alpha-pregnan-20-one to estrogen-primed ovariectomized rats. A single injection of 2 or 4 mg progesterone, 4 mg 5 alpha-dihydroprogesterone, or 4 mg 3 alpha-hydroxy-5 alpha-pregnan-20-one 72 h (Day 3) after estrogen pretreatment induced a highly significant increase in serum LH and FSH 6 h later (1800 h). Although serum gonadotropin levels had begun to decrease 12 h after administration of the progestins, they were still significantly higher than control values and did not return to baseline levels until noon on Day 4. When either progesterone or 3 alpha-hydroxy-5 alpha-pregnan-20-one was administered at noon on Days 3 and 4, there was a significant reduction in LH levels 6 h after the second injection. In contrast, serum LH levels were slightly elevated 3 to 6 h (1500 to 1800 h) after the second injection of 5 alpha-dihydroprogesterone and did not decrease until 2100 h. There was no effect on FSH concentrations after a second injection of any of the progestins. Loss of uterine luminal fluid was observed within 24 h after a single injection of progesterone. Neither of the 5 alpha-reduced metabolites had an effect on uterine ballooning until after the second injection, and, even then, nonfluid-filled uteri were observed in only 20 to 30% of the animals. The results suggest that the conversion of progesterone to 5 alpha-dihydroprogesterone and 3 alpha-hydroxy-5 alpha-pregnan-20-one by neuroendocrine tissues may be necessary for the positive and negative feedback effects of progesterone on gonadotropin secretion. Thus, the diverse effects of progesterone may be due to progesterone per se (e.g., in the uterus) and/or its metabolites (e.g., in the hypothalamus and pituitary).

Intracerebral implantation of progesterone: Re-examination of the brain sites responsible for facilitation of sexual receptivity in estrogen-primed ovariectomized rats

Ovariectomized female rats were tested for sexual receptivity following SC priming with threshold doses of estradiol benzoate and intracerebral 27 ga implants of either progesterone or cholesterol. All females were repeatedly tested under both intracerebral hormone implant conditions. Cholesterol implants failed to activate receptivity, while progesterone implants in the interpeduncular-ventral tegmental area produced near maximal levels of receptivity within 30 min after implantation. Progesterone implants in the medial hypothalamus, anterior hypothalamus, preoptic area, pons, mesencephalic reticular formation and lateral mesencephalon failed to activate sexual receptivity.

Induction of lordosis in female rats: Two modes of estrogen action and the effect of adrenalectomy

In ovariectomized female rats, progesterone treatment alone does not induce lordosis, but following estrogen treatment by an appropriate interval it greatly enhances the performance of lordosis compared to that with estrogen alone. This “facilitating” effect of progesterone is thought to act synergistically with the initial “priming” effect of estrogen. In the present experiments a second estrogen treatment given to estrogen-primed ovariectomized rats in place of progesterone was found to facilitate lordosis. Latency of the facilitation of lordosis following this second estrogen treatment was similar to that of progesterone and was much shorter than that required for the usual “priming” effect, but higher doses were needed for the “facilitatory” effect. Experiments with adrenalectomized-ovariectomized female rats showed that this short latency effect of second estrogen treatment need not be mediated by the adrenals. These results raise the possibility that estrogen acts on the central nervous system in more than one way to induce lordosis.

Potassium Chloride-Induced Lordosis Behavior in Rats Is Mediated by the Adrenal Glands

Potassium chloride applied topically to the neocortex facilitates lordosis behavior in estrogen-primed ovariectomized rats. This effect is absent in rats that are also adrenalectomized. Potassium chloride fails to facilitate lordosis in estrogen-primed rats, with intact adrenals, which are pretreated with dexamethasone, an inhibitor of the release of adrenocorticotropic hormone. Adrenalectomized rats that have been treated with dexamethasone are capable of responding to progesterone with the display of lordosis. The results suggest that application of potassium chloride to the neocortex acts as a stressor that causes the release of adrenal progestin.

The stimulatory effect on gonadotropin release of implants of estradiol or progesterone in certain sites in the central nervous system.

The sites of stimulatory feedback of ovarian steroids on gonadotropin release were examined. In estrogen-primed ovariectomized rats, estradiol or progesterone was implanted stereotaxically into various hypothalamic and extrahypothalamic areas. Both steroids elevated plasma LH and FSH levels at 6 h when implanted unilaterally into the preoptic-anterior hypothalamic area. Bilateral implants at this site were ineffective; presumably, this was due to the destructive lesion produced by the cannulae since in sham-implanted or anteriorly deafferented rats systemic estrogen was also ineffective. Unilateral estradiol implants in the medial basal hypothalamus elevated LH and FSH at 30 but not at 6 h. Maximum increases of plasma gonadotropins occurred 30 h after implantation of estradiol in the medial amygdaloid nuclei; progesterone implants at this site elevated only FSH at 6 h. Dissociation in the release of LH and FSH was also observed following implantation of estradiol into the hippocampus. Plasma FSH levels were dramatically reduced at 30 h while LH was slightly elevated. Progesterone implants in the hippocampus or medial basal hypothalamus did not alter plasma gonadotropin levels.

Uterine responsiveness to estrogen in 4-day cycling and in estrogen-primed ovariectomized rats as assessed by uptake and incorporation of (3H) leucine.

The degree of uterine responsiveness to exogenous estrogen was studied in 4-day cycling rats and in ovariectomized, estrogen-primed rats. Uterine tissue collected at different stages was incubated in medium-199 containing [3H]leucine at 37 C under 95% oxygen and 5% carbon dioxide for 2 hr. Tissue uptake and protein incorporation of the radioactivity were measured to assess uterine activity. In cycling rats, the uterus was able to respond to 1.0 µg of 17β-estradiol by increases in both uptake and incorporation of [3H] leucine during estrus, metestrus and in the morning of diestrus but not during proestrus nor in the afternoon of diestrus. In ovariectomized rats, estrogen priming (1.0 µg) seemed to cause an immediate loss in uterine sensitivity to further hormonal stimulation. Subsequently, the estrogen-primed uterus gradually regained its estrogen responsiveness and eventually reached a degree even higher than that of unprimed uterus. The data suggest that the ability of the uterus to respond to exogenous ...

Effects of cortical stimulation on estrous behavior in estrogen-primed ovariectomized rats.

Sexual receptivity was facilitated in estrogen-primed, ovariectomized female rats by applying current to the cortex with chronically implanted bipolar silver ball electrodes. The rats were primed with 2 μg of estradiol benzoate per day for 3 days and on the fourth day given a sexual behavior test in which male rats were allowed to mount each female 10 times. The number of lordosis responses was used as an index of estrous behavior and expressed as a lordosis quotient. The EEG was monitored before and after cortical stimulation. There was a significant increase in the lordosis quotient after 400 μA (5-sec train of monophasic rectangular pulses, 20 cps, 0.1 msec) had been applied to the cortex, and the animals displayed EEG after discharge activity, hyperlordosis responses and increased behavioral sensitivity to vaginal stimulation with a glass rod. In estrogen-primed rats cortical stimulation at 400 μA was sufficient to produce, after a latency of 5 min, a degree of sexual receptivity which was comparable to that seen in estrogen-progesterone primed rats and which lasted for at least 2 hr. Since electrical stimulation of the cerebral cortex effectively replaces progesterone in the facilitation of sexual behavior in the female rat, it is suggested that progesterone action may involve an alteration in cortical function. (Endocrinology93: 20, 1973)

Effects of luteinizing hormone on multiple-unit activity in the rat hippocampus.

In estrogen-primed ovariectomized rats under urethane anesthesia, multiple-unit electrical activity (MUA) in the subiculum of the ventral hippocampus responded to intravenous injection of luteinizing hormone (LH) with an increased level of activity in about half of the cases; the others showed no change. Similar responses were observed in the arcuate nucleus-median eminence region of the hypothalamus, although some decreases in MUA were also observed there. The positive hippocampal response was not induced by FSH, TSH, or boiled LH. It is suggested that LH receptors may exist in the subiculum and that the effect is transmitted to the hypothalamus by the medial corticohypothalamic tract.