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Biomedical subjects

H H Feder

Publications and source records attributed to H H Feder.

At least 55 records · Page 3Linked to original sources

Estradiol and progesterone influence L-5-hydroxytryptophan-induced myoclonus in male guinea pigs: sex differences in serotonin-steroid interactions.

The effects of castration in males and sex differences in the effects of estradiol and progesterone on L-5-hydroxytryptophan (L-5-HTP)-induced myoclonus in guinea pigs were examined. Castration had no effect on L-5-HTP-induced myoclonus in males. There were sex differences in sensitivity to L-5-HTP. In the absence of steroids, L-5-HTP-induced myoclonus was higher in gonadectomized males than females. A low dose of estradiol benzoate (EB; 3.5 micrograms) given 46 h before L-5-HTP (100 mg/kg) enhanced myoclonus in gonadectomized females but not males. However, at a higher dose of EB (10 micrograms) and a lower dose of L-5-HTP (80 mg/kg), myoclonic responding was enhanced in males. These findings indicate that estradiol has a similar effect on L-5-HTP-induced myoclonus in males and females, but do not rule out the possibility of sex differences in sensitivity to L-5-HTP when both sexes are given estradiol priming. When L-5-HTP was given 6 h after 0.5 mg progesterone in estradiol-primed males, myoclonus was enhanced. Progesterone treatment reverses the facilitative effect of EB on L-5-HTP-induced myoclonus in females. Therefore, progesterone has opposite effects on L-5-HTP-induced myoclonus in males and females. These findings were discussed with respect to the interaction of steroids and 5-HT transmission in the regulation of steroid-dependent reproductive behavior.

5-Hydroxytryptophan↗

Nonluteal source of lordosis-promoting progesterone secretion in guinea pigs.

Prepubertal (21-24 days of age), intact female guinea pigs treated sequentially with estradiol benzoate and LH or FSH displayed lordosis behavior. The gonadotropins apparently caused release of progesterone from the ovaries, because lordosis behavior in guinea pigs is activated by sequential action of estrogen and progesterone. These data demonstrate that immature ovaries, completely devoid of corpus luteum tissue, are capable of secreting behaviorally significant concentrations of progesterone when stimulated by gonadotropins. Therefore, the luteal compartment of the guinea pig ovary is not essential for the preovulatory surges of progesterone that coincide with expression of lordosis behavior in adulthood. Likely candidates for sources of preovulatory progesterone in prepubertal females are antral follicle and interstitial gland tissue.

Animals↗

Alpha 1-noradrenergic regulation of hypothalamic progestin receptors and guinea pig lordosis behavior.

Experiments were conducted to determine whether alpha 1- or alpha 2-receptors mediate noradrenergic (NA) regulation of guinea pig lordosis behavior and hypothalamic progestin receptors. When infused into a lateral cerebroventricle at a dose that inhibits lordosis and that decreases the concentration of estradiol-inducible hypothalamic progestin receptors, phenoxybenzamine decreased binding of the alpha 1-ligand [3H]WB4101 but not the alpha 2-ligand [3H]clonidine to brain membranes. Thus, under the conditions used, phenoxybenzamine appears to block alpha 1-receptors with little or no effect on alpha 2-receptors. Experiments with the selective alpha 1-antagonist prazosin also indicated alpha 1-receptor regulation of lordosis and hypothalamic progestin receptors. Prazosin inhibited lordosis induced by estradiol benzoate (EB) plus progesterone and by EB + clonidine and decreased the concentration of cytoplasmic progestin receptors in hypothalamus (but not in preoptic area or frontal cortex) of EB-primed females. The inhibition of lordosis is apparently not due to some unknown side effect of prazosin because pretreatment with a high dose of clonidine attenuated the inhibition. The possibility that a causal relationship exists between effects of alpha 1-NA transmission on hypothalamic progestin receptors and lordosis was discussed. Also, because effects of NA transmission on hypothalamic progestin receptors are dependent on prior treatment with EB, it was suggested that NA transmission might influence estradiol action in addition to progestin action in hypothalamic cells.

Animals↗

Estradiol and progesterone influence a serotonin mediated behavioral syndrome (myoclonus) in female guinea pigs: comparison with steroid effects on reproductive behavior.

L-5-hydroxytryptophan (L-5-HTP)-induced myoclonus was used as a behavioral index of central serotonergic activity. Estradiol benzoate (EB) and progesterone (P) influenced the induction of myoclonus by L-5-HTP. When L-5-HTP was injected 46 h after EB, myoclonus was enhanced. P blocked this effect on EB when 100 or 125 mg/kg L-5-HTP (but not 80 mg/kg) was given 6 h after P in EB-primed animals. When L-5-HTP was given 3 or 11-15 h after P in EB-primed animals, there was no inhibitory effect of P on myoclonus. In fact, at the lowest dose (80 mg/kg), L-5-HTP increased myoclonus when given 3 h after P in EB-primed animals. The inhibitory effects of P in EB-primed females on myoclonus were temporally correlated with the display of lordosis, suggesting that the neural progestin receptor mechanisms that have been proposed to mediate P effects on lordosis are also involved in the inhibitory effects of P on myoclonus.

5-Hydroxytryptophan↗

Lack of an effect of estrogen on endogenous RNA polymerase II in guinea pig brain.

An early action of estrogen in peripheral target tissues is to increase endogenous RNA polymerase II activity which precedes changes in protein synthesis. Previous reports have indicated that estrogen causes a similar increase in polymerase activity in rat brain regions containing high affinity receptors for this hormone. The present series of experiments was designed to test whether a similar action of estrogen on polymerase activity occurs in guinea pig brain, with the expectation being that this enzyme might prove to be a useful marker for the early actions of estrogen. Injections of 25 or 100 micrograms estradiol-17 beta in an ethanol-saline vehicle failed to induce significant changes in polymerase II activity in the basal hypothalamus, preoptic area-septum or cortex 1, 2, 6, 13 or 24 h after hormone administration. It is concluded that the modification of RNA polymerase II activity by estrogen is not a good marker for estrogen action in the brain. This may be due to the intrinsic heterogeneity of the tissue resulting possibly in (1) increased activity in some cells and decreased activity in other cells with no net change in overall polymerase activity after estrogen treatment (2) only a small percentage of the cells responding to the steroid with altered polymerase activity with this change not detectable when whole tissue is measured or (3) only a few genes within the cells being altered in transcription by the steroid.

Animals↗

Administration of estradiol-17 beta in pulses to female guinea pigs: self-priming effects of estrogen on brain tissues mediating lordosis.

Lordosis behavior in ovariectomized guinea pigs is facilitated by the sequential action of estradiol-17 beta (E) and progesterone (P). The present study was designed to explore the possibility that administration of E in a pulsatile manner is more efficacious than a single injection of E with respect to lordosis facilitation in ovariectomized guinea pigs. The data indicate that pulse administration of unesterified E is more effective than a single large dose of E for the facilitation of lordosis behavior. Three injections of as little as 0.5 microgram E at 0, 19 and 28 hr followed by 0.5 mg P at 39 hr was more effective (63.6% responding with lordosis) than a single injection of as much as 15 micrograms E at hr 0 followed by vehicle injections at 19 and 28 hr and 0.5 mg P at 39 hr (0% responding). We also demonstrated that the 19 hr E injection could be eliminated and that two injections of E (0.5 microgram at hr 0 and 1.0 microgram at hr 28 followed by 0.5 mg P at hr 39) was at least as effective (69.0% responding) as three split injections in facilitating lordosis. This behaviorally effective pulse administration of E also resulted in significant induction of cytoplasmic progestin receptors in hypothalamic tissue. Further experiments indicated that a 28 hr interval between E pulses was optimal in terms of percent animals displaying lordosis. The data suggest that pulsatile E stimulation of brain tissues mediating lordosis is a highly effective mode of stimulation, and that an initial pulse of E sensitizes neural tissues to subsequent E administration.

Animals↗

Development of steroid-receptor systems in guinea pig brain. I. Cytoplasmic estrogen receptors.

The development of the cytoplasmic estrogen receptor (CER) system in male and female guinea pigs was examined to determine whether attainment of sensitivity to estrogen action related to lordosis behavior is correlated with increases in brain CER concentrations. Ovariectomized neonatal (7 days old) guinea pigs failed to display lordosis after priming with 10 micrograms estradiol benzoate (EB) and 0.5 mg progesterone (P). The percentage of ovariectomized steroid-treated females displaying lordosis increased at 29-33 days of age. At 50-65 days of age this percentage increased even further. Plasma levels of estrogen in 4-6 day old animals at 4, 8 and 12 h after 10 micrograms EB were at least equal to those seen in 50-65 day old animals. Neither the concentration nor the affinity of CER in hypothalamus (HYPO), preoptic area (POA), amygdala (AMYG) and cortex ( CORT ) were different in 4-6 day olds vs 50-65 day olds. The rank order for concentrations of CER in brain regions was: POA greater than HYPO greater than AMYG greater than CORT . A sex difference in CER was found in HYPO (females greater than males), but not POA, AMYG or CORT of 4-6 day olds.

Animals↗

Development of steroid-receptor systems in guinea pig brain. II. Cytoplasmic progestin receptors.

The development of the cytoplasmic progestin receptor (CPR) system in male and female guinea pigs was examined to determine if insensitivity to the lordosis promoting activity of estrogen-progestin treatment in adult males and neonatal guinea pigs is correlated with alterations in this receptor system. Gonadectomized neonatal (4-6 days old) and adult (50-65 days old) guinea pigs of both sexes were injected with estradiol benzoate (EB) and killed 40 h later. CPRs were measured in the hypothalamus (HYPO), preoptic area (POA) and cortex ( CORT ). Neonatal brain contained both high (Kd congruent to 0.1 nM) and low (Kd greater than 10 nM) affinity binders for [3H]R5020 similar to those found in adult brain. In the absence of EB-priming the concentration of CPR in HYPO, POA and CORT was lower in neonatal animals than adults. In both males and females, neither a low (1.6 micrograms) nor a high (10 micrograms) dose of EB resulted in a concentration of estrogen inducible CPR in neonatal HYPO greater than that found in adult HYPO after 1.6 micrograms EB. Even after treatment with 50 micrograms EB the concentration of CPR in neonatal female HYPO was not different from adult female HYPO after 1.6 micrograms EB. In neonatal POA, 10 micrograms EB resulted in a concentration of CPR greater than that found in adult POA after 1.6 micrograms EB. Finally, there was a sex difference in the concentration of estrogen inducible CPR in HYPO (female greater than male) but not POA of adult guinea pigs. No sex difference in CPR concentration was found in any neonatal brain area.

Aging↗

Development of steroid-receptor systems in guinea pig brain. III. Nuclear progestin receptors.

Nuclear progestin receptors (NPR) were measured, with an exchange assay, in neonatal (4-6 days old) and adult (50-60 days old) guinea pigs of both sexes in order to further examine deficits in the neonatal hypothalamic progestin receptor system. Both neonatal and adult hypothalamus (HYPO) and cortex ( CORT ) contained a KCl extractable high affinity (Kd congruent to 0.1 nM) binder for R5020. In neonatal guinea pigs, given 10 micrograms estradiol benzoate (EB), NPR accumulation in HYPO and CORT peaked 2-4 h after a 0.5 mg injection of progesterone (P). There was no dose response of NPR to EB in neonatal HYPO, CORT or adult CORT . In adult HYPO, 10 micrograms EB-priming resulted in a higher concentration of NPR than 1.6 micrograms EB-priming. Neonatal HYPO (1.6 or 10 micrograms EB) did not differ in concentration of NPR from adult HYPO (1.6 micrograms EB). Neonatal CORT (1.6 or 10 micrograms EB) showed a lower NPR concentration than adult CORT (1.6 micrograms EB). There was a sex difference (females greater than males) in NPR concentration in both neonatal and adult HYPO, but not CORT . These results are discussed with regard to deficits in cytoplasmic progestin receptors and behavioral insensitivity to estrogen-progestin treatment found in neonatal guinea pigs.

Animals↗

Characteristics of [3H]prazosin binding to guinea pig brain alpha-adrenergic receptors: effects of estradiol and progesterone.

[3H]Prazosin was found to bind to sites on guinea pig brain membranes with alpha 1-adrenergic receptor characteristics. Treatment of ovariectomized guinea pigs with estradiol benzoate (EB) or EB followed by progesterone (P) did not affect [3H]prazosin binding to membranes from hypothalamus, preoptic area, amygdala or cerebral cortex. When added to the incubation mixture of the assay, estradiol, P, and other steroids decreased [3H]prazosin binding but only at high concentrations. These results do not support the idea that estrogen and progestin influence reproductive physiology through effects on brain alpha 1-receptors, although limitations of the methodology employed do not completely rule out this possibility.

Animals↗

Effects of serotonin agonists on lordosis, myoclonus, and cytoplasmic progestin receptors in guinea pigs.

Peripheral treatment with the serotonin releaser fenfluramine or the serotonin agonist quipazine abolished lordosis behavior in ovariectomized estradiol and progesterone-primed female guinea pigs. Quipazine was also effective when administered into a lateral cerebral ventricle. The lowest dose of fenfluramine that induced myoclonus (10 mg/kg) was higher than the dose needed to inhibit lordosis (5 mg/kg). Therefore, it appears that myoclonus and lordosis are differentially sensitive to serotonin agonists. The effects of quipazine on lordosis were time dependent. Quipazine had no effect on lordosis when given prior to the onset of sexual receptivity. These data suggest that serotonin agonists might be effective only when progesterone has had sufficient time to induce sexual receptivity. Quipazine did not affect cytoplasmic progestin receptors in brain areas involved in steroid hormone effects on lordosis. This finding, and the finding that quipazine had no effect on lordosis when given prior to the onset of sexual receptivity, suggest increased serotonin transmission does not interfere with estrogen priming or sensitivity of hypothalamic cells to progesterone.

Animals↗

Long-term (39--51 hr) exposure to estradiol in silastic capsules and lordosis behavior of guinea pigs.

Three dosage levels of estradiol (E2) in Silastic capsules were administered to ovariectomized guinea pigs for periods of 39 or 51 hr. At 39 hr., a systemic injection of progesterone was given, and hourly testing began. Dose-dependency of various aspects of lordosis behavior was established at both time intervals, and the serum E2 levels produced by the medium and high dosage levels bracketed those found at the proestrus peak in intact guinea pigs. Although there were no significant behavioral differences between the 39- and 51-hr groups at the individual dosage levels, when the data from all three dosage groups were collapsed, exposure for 51 rather than 39 hr was seen to produce increases in maximum lordosis and heat-duration measures. The results suggest that subtle facilitative effects of estrogen occur very late in the estrogen-conditioning process (even after progesterone is administered).

Animals↗

Effects of neonatal estrogen treatment of female guinea pigs on mounting behavior in adulthood.

Female guinea pigs were treated with 200 micrograms estradiol dipropionate (ED) daily from Days 1 to 15 of life. As adults they all ovulated. After gonadectomy and estrogen-progesterone treatment in adulthood, lordosis behavior was evident and showed no decrements (compared with neonatally oil-treated controls) except for a marginal decrease in maximum duration scores. However, testosterone propionate treatment in adulthood significantly increased mounting behavior in neonatally ED-treated females compared to the controls. On the other hand, estrogen-progesterone treatment in adulthood stimulated mounting in the neonatally oil-treated group, but not in the neonatally estrogenized group. The results suggest that at least some aspects of steroid-dependent behaviors can be permanently influenced by estrogen treatment after the presumed prenatal critical period for sexual differentiation has been completed in guinea pigs.

Age Factors↗