Expression of Fos within luteinizing hormone-releasing hormone neurons, in relation to the steroid-induced luteinizing hormone surge in guinea pigs.

The induction of Fos protein was examined within LHRH neurons of guinea pigs; the aim was to delineate relationships between subgroups of LHRH neurons during an LH surge in a laboratory rodent in which the distribution of LHRH neurons and the presence of a true luteal phase in the reproductive cycle resemble those in primates. Approximately one third of the forebrain population of LHRH neurons was examined in ovariectomized steroid-treated guinea pigs killed either before or during a steroid-induced LH surge. LHRH/Fos double-labeled neurons were more abundant in surging compared to presurge guinea pigs (p = 0.008) and were most abundant within the preoptic area and anterior hypothalamus. Nonetheless, double-labeled LHRH/Fos neurons were observed throughout the remainder of the population of LHRH neurons in surging guinea pigs. A relative loss of LHRH reaction product was detected by image analysis in the LHRH terminals in the median eminence of surging guinea pigs, consistent with augmented LHRH release. Thus, there appears to be a coordinated increase in Fos expression in subgroups of LHRH neurons, more pronounced in rostral, as compared to caudal, regions in guinea pigs killed after the peak of the steroid-induced LH surge.

A subgroup of LHRH neurons in guinea pigs with progestin receptors is centrally positioned within the total population of LHRH neurons.

Although the role of gonadal steroids in inducing the LH surge is undisputed, the mechanism(s) whereby steroids induce the release of the hypothalamic luteinizing hormone-releasing hormone (LHRH) remain(s) enigmatic. In this study we examined the issue of the presence of steroid receptors in LHRH neurons using a mammalian species that has a true luteal phase, namely, guinea pigs. Progestin receptors (PR) were localized in LHRH neurons of ovariectomized guinea pigs administered estradiol (10-20 micrograms estradiol benzoate) for 3-4 days, using several different immunocytochemical protocols. The subgroup of LHRH neurons containing PR, although small, was strategically positioned within the core of the total population of LHRH neurons. This central position was visualized in simultaneous views of three-dimensional computer reconstructions of the populations of LHRH/PR neurons and LHRH neurons. The subgroup of LHRH/PR neurons formed a thread permeating the population of LHRH neurons. We propose that in guinea pigs, LHRH neurons containing progestin receptors, are foci of activity, capable of activating a larger component of the LHRH population of cells in certain endocrine conditions, such as prior to the LH surge.

Central prolactin infusions stimulate maternal behavior in steroid-treated, nulliparous female rats.

A series of experiments were conducted to determine whether and under what conditions central prolactin (PRL) administration would stimulate the onset of maternal behavior in female rats and to identify possible neural sites of PRL action. In each experiment ovariectomized, nulliparous rats whose endogenous PRL levels were suppressed with bromocriptine were tested for maternal behavior toward foster young. In experiments 1, 2, and 4, females were also exposed to pregnancy-like levels of progesterone (days 1-11) followed by estradiol (days 11-17). In experiment 1 infusions (days 11-13) of four doses of ovine PRL (400 ng, 2 micrograms, 10 micrograms, or 50 micrograms, but not 80 ng) into the lateral ventricle resulted in a rapid onset of maternal behavior (behavioral testing, days 12-17). The stimulatory action of these doses of PRL appears to be central, since subcutaneous injections of 50 micrograms of ovine PRL failed to affect maternal responsiveness (experiment 2). Experiment 3 indicated that the stimulatory effect of intracerebroventricularly administered PRL is steroid dependent. Infusions of either 10 micrograms of ovine PRL or 10 micrograms of rat PRL failed to induce maternal behavior in nonsteroid-treated animals. In the final experiment (no. 4) bilateral infusions of 40 ng of ovine PRL into the medial preoptic area of steroid-treated rats resulted in a pronounced stimulation of maternal behavior. These findings demonstrate a central site of PRL action in the stimulation of maternal responsiveness and point to the medial preoptic area as a key neural site for PRL regulation of maternal behavior.

Prolactin (PRL) regulation of maternal behavior in rats: bromocriptine treatment delays and PRL promotes the rapid onset of behavior.

Recent findings indicate that PRL helps stimulate the onset of maternal behavior in inexperienced hypophysectomized steroid-treated female rats. In a series of five experiments we have further examined the involvement of PRL in maternal behavior using nonhypophysectomized ovariectomized rats treated concurrently (type I) or sequentially (type II) with progesterone (P) and estradiol (E2) and administered either bromocriptine (to suppress endogenous PRL secretion) or bromocriptine plus ovine PRL. In Exp 1 plasma PRL concentrations were measured in ovariectomized rats treated for 2 weeks with a combination of E2 and P Silastic implants. Type I steroid-treated (2mm E2, days 1-24; three 30 mm P, days 3-13) rats exhibited elevated plasma PRL levels throughout the sampling period compared with nonsteroid-treated controls. In contrast, PRL concentrations in type II steroid-treated (P, days 3-13; E2, days 13-24) females were low (similar to controls) from days 3-13 when the type II steroid-treated females were exposed to P only. Like type I treated rats, PRL levels in type II steroid-treated rats were elevated from day 13 onward after E2 capsule insertion. In Exp 2, treatment of both type I and type II steroid-treated rats with bromocriptine (2 mg/kg, sc) twice daily beginning on treatment day 13 suppressed basal PRL concentrations and prevented the estrogen-induced diurnal PRL surge. Whereas PRL was effectively suppressed by bromocriptine in both steroid-treated groups, the absolute levels of PRL were lower in rats treated with the type II steroid regimen. Behavioral analyses in Exp 3, 4, and 5 revealed that bromocriptine administration, while failing to interfere with the onset of maternal behavior in rats treated with the type I concurrent steroid regimen, disrupted the onset of maternal care in rats treated with the type II sequential steroid regimen. When a separate set of type II steroid-treated rats was given both bromocriptine (2 mg/kg) plus ovine PRL (0.5 mg, sc) twice daily, maternal behavior rapidly appeared. Thus, suppression of endogenous PRL secretion delays the onset of maternal behavior in nonhypophysectomized steroid-primed rats, an effect prevented by concurrent administration of ovine PRL. In addition to providing further experimental support for PRL's role in maternal behavior, the development of this endocrine regimen provides researchers with a potentially fruitful model to examine neural sites and mechanisms of PRL regulation of maternal behavior in mammals.

Long-term effects of parity on opioid and nonopioid behavioral and endocrine responses.

Parity (number of parturitions) affects the endogenous opioid system. Multiparous lactating rats are less sensitive to the effects of morphine (MOR) on maternal behavior (MB) and analgesia than primiparous lactating rats. In order to determine whether these changes in opiate sensitivity persist beyond the lactational state, the present study compared the sensitivity of ovariectomized nulliparous and nonlactating primiparous rats to MOR's effects on MB (Experiment 1), analgesia (Experiment 2) and prolactin release (Experiment 3) in addition to stress-induced analgesia (Experiment 2). In Experiments 1 and 2 primiparous rats were allowed to give birth and remain with their litter (culled to 6 pups) until weaning. At that time the pups were removed and the dams and age-matched nulliparous rats were ovariectomized. Four weeks later animals were exposed to foster pups daily in order to induce MB (Experiment 1). On day 5 or 6 of full MB the primiparous and nulliparous rats received either saline or one of four doses of MOR (0.625, 1.25, 2.5, or 5.0 mg/kg, SC) and 60 min later MB was assessed. MOR, at the 2.5 mg/kg dose, disrupted MB in a significantly greater percentage of nulliparous as compared to primiparous animals (100% vs. 55%, respectively). In Experiment 2, nulliparous and nonlactating primiparous animals received 2.5 mg/kg of MOR four weeks after ovariectomy. Analgesia was assessed on a tail-flick apparatus 30, 60, 90, 120 and 150 min postinjection. One week later the same animals were exposed to cold-water swims (CWS, 2 degrees C, 3.5 min) and tail-flick latencies were again recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoreactive beta-endorphin concentrations in brain and plasma during pregnancy in rats: possible modulation by progesterone and estradiol.

Changes in opioid concentrations in brain and plasma as well as opioid activity have been reported to occur as a function of pregnancy and lactation in rats. The present study examines the status and steroidal regulation of the endogenous opioid, beta-endorphin, in the behaviorally and neuroendocrinologically important preoptic area (POA) and hypothalamus, and in the plasma of pregnant and nonpregnant rats. In the first study, concentrations of beta-endorphin-like immunoreactivity (beta-EP-LI-Ir) in POA and hypothalamic tissues as well as in plasma were measured throughout gestation in rats. beta-EP-LI-Ir concentrations in the POA were significantly higher in rats from day 6 to 18 of gestation than in nonpregnant, diestrous females. beta-EP-LI-Ir concentrations in the POA declined significantly between day 18 and 22 of gestation. Changes in hypothalamic beta-EP-LI-Ir concentrations were not detected either as a function of pregnancy or during pregnancy, while plasma beta-EP-LI-Ir concentrations declined gradually from day 6 to 18 of pregnancy and then increased significantly prepartum (day 22 of gestation). In the second study, the effects of 2 weeks of exposure to pregnancy levels of progesterone and estradiol on brain and plasma beta-EP-LI-Ir were measured. Exposure to the combination of progesterone and estradiol (administered subcutaneously via Silastic capsule implants) resulted in a significant increase in beta-EP-LI-Ir concentrations in the POA, but did not affect beta-EP-LI-Ir concentrations in either the hypothalamus or plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Light intensity and the control of melatonin secretion in rats.

The effect of varying ambient light intensity on the phase and amplitude of urinary melatonin rhythms was studied in rats housed individually in metabolism cages. For 17 days one group (D) was exposed to alternating 12-hour periods of dim light (0.1-0.3 micro/cm2) and total darkness; a second group (L) was exposed alternately to dim light and bright ligh (45-110 micro/cm2). All animals were then exposed to constant dim light for 15 days, after which they were returned to their original lighting regimens (D or L). 18 days later, half of each group was killed at the midpoint of the dim light phase, and the other half 12 h later. Both groups excreted melatonin rhythmically when exposed to daily cycles in light intensity; the L animals excreted 69% of the total daily melatonin output during the dim light phase and the D group of rats excreted 70% during the dark phase. When placed under continuous dim light, L animals continued to excrete melatonin as before, but D rats excreted significantly less, and the melatonin rhythm was dampened. When returned to a diurnal light cycle, both groups again exhibited rhythms in melatonin excretion that were entrained to the light cycle. Animals killed at the time of day coinciding with diminished melatonin excretion had lower pineal and serum melatonin levels (0.2 +/- 0.1 ng/pineal; 30 +/- 8 pg/ml serum) than those killed 12 h later (2.0 +/- 0.4 ng/pineal; 57 +/- 20 pg/ml serum). These observations provide additional evidence that measurement of urinary melatonin levels gives an accurate index of melatonin secretion from the rat pineal. They also show that a given light intensity presented for a part of the 24-hour day (e.g., dim light; 0.1-0.3 micro/cm2) can be interpreted by the mammalian pineal as light or dark, depending on the light intensity available during the rest of the day.