Stimulation Of Medial Preoptic Area Research Articles

Inactivation of the periaqueductal gray attenuates antinociception elicited by stimulation of the rat medial preoptic area

The medial preoptic area (MPOA) is a sexually dimorphic structure that plays key roles in gonado-steroidal regulation and thermoregulation. The MPOA may be involved in sex-based differences in nociceptive processing and steroid hormones effect on pain thresholds. Consistent with this, there is evidence that MPOA can produce antinociception or hyperalgesia. MPOA stimulation inhibits spinal cord or trigeminal neuronal responses to noxious stimuli or produces analgesia, yet most of these studies utilized electrical stimulation which antidromically activates periaqueductal gray (PAG) and rostroventromedial medulla (RVM) neurons involved in descending modulation of nociception. Effects of selective activation of MPOA neurons on behavioral indices of antinociception and the site-specificity of such responses are unknown. To address these questions, we examined the influence of MPOA microinjections of d,l homocysteate (DLH) on hindlimb and tail nocifensive reflexes in lightly anesthetized rats. DLH, but not saline, microinjections into several MPOA subregions markedly increased withdrawal response latencies to noxious thermal stimuli. Antinociceptive effects of MPOA activation were abolished by microinjection of lidocaine into PAG. These results suggest that activation of MPOA neurons produces antinociception that is at least partly mediated by projections to PAG.

Dopamine, the medial preoptic area, and male sexual behavior

The medial preoptic area (MPOA), at the rostral end of the hypothalamus, is important for the regulation of male sexual behavior. Results showing that male sexual behavior is impaired following MPOA lesions and enhanced with MPOA stimulation support this conclusion. The neurotransmitter dopamine (DA) facilitates male sexual behavior in all studied species, including rodents and humans. Here, we review data indicating that the MPOA is one site where DA may act to regulate male sexual behavior. DA agonists microinjected into the MPOA facilitate sexual behavior, whereas DA antagonists impair copulation, genital reflexes, and sexual motivation. Moreover, microdialysis experiments showed increased release of DA in the MPOA as a result of precopulatory exposure to an estrous female and during copulation. DA may remove tonic inhibition in the MPOA, thereby enhancing sensorimotor integration, and also coordinate autonomic influences on genital reflexes. In addition to sensory stimulation, other factors influence the release of DA in the MPOA, including testosterone, nitric oxide, and glutamate. Here we summarize and interpret these data.

Lesions of the periaqueductal gray block the medial preoptic area-induced activation of the urethrogenital reflex in male rats

The medial preoptic area (MPOA) is important for male sexual behavior, including erections and ejaculation. Stimulation of the MPOA evokes urethrogenital reflex-like responses. However, the descending pathways mediating this response are unknown. We examined the effect of bilateral lesions of the periaqueductal gray (PAG) on the MPOA-induced response. Electrical stimulation of the MPOA was used to induce rhythmic motor patterns of the bulbospongiosus muscle, discrete regions of the PAG were lesioned and the response to MPOA stimulation re-examined. These studies demonstrate that the descending pathway mediating the MPOA-induced activation of the urethrogenital reflex-like responses travel through and may relay in the PAG.

Differential ICP responses elicited by electrical stimulation of medial preoptic area

Differential ICP responses elicited by electrical stimulation of medial preoptic area

Steroidal control of male hamster sexual behavior in Me and MPOA: effects of androgen dose and tamoxifen

Steroids stimulate male sexual behavior through interconnected limbic nuclei, including the medial amygdala (Me) and medial preoptic area (MPOA). Although Me and MPOA each can transduce hormonal cues to induce sexual activity in castrated male hamsters, simultaneous stimulation of Me and MPOA fails to amplify mating. The present study extends our investigations of redundancy in the hormonal control of mating by testing the behavioral effects of (1) increasing steroid dose in a single brain region or (2) locally blocking steroid action with an estrogen antagonist. In Experiment 1, sexually experienced castrates received a single testosterone implant in Me, bilateral testosterone implants, or a single implant of a highly potent androgen, 7a-methyl-19-nortestosterone (MENT). These treatments stimulated mating behavior: 2 weeks after surgery, mounting was observed in ≥50% of the males in each group. In Experiment 2, castrated males received intracerebral implants of the estrogen antagonist tamoxifen in Me or MPOA, combined with systemic testosterone replacement. Tamoxifen in MPOA had minimal effects on the recovery of mating behavior. With tamoxifen in Me, mounts and intromissions were significantly reduced 18 days after surgery. However, the percent of males in each group that expressed mounts, intromissions or ejaculations was not different. Thus, in Experiment 1, increasing the amount of steroid does not amplify mating. Likewise, local blockade of hormone action in Experiment 2 does not prevent behavior. These findings support the concept that steroids are largely permissive for male sex behavior. Steroid stimulation of either Me or MPOA is sufficient for sexual activity. Conversely, neither Me nor MPOA has an absolute requirement for hormones to facilitate expression of mating.

Differential ICP responses elicited by electrical stimulation of medial preoptic area.

Recent findings indicate a complex role for the medial preoptic area (MPOA) in modulating penile erection. To further investigate this important area we measured changes in intracavernous pressure (ICP) elicited by electrical stimulation of the MPOA and evaluated the contribution of the cavernous nerve to the ICP responses after bilateral transection of the cavernous nerve (CN). In all experiments electrical stimulation was performed unilaterally in anesthetized male rats. Two distinct patterns of ICP response were seen after electrical stimulation of the MPOA: 1) increases in ICP during electrical stimulation (pattern 1, n = 10 rats) and 2) increases in ICP after electrical stimulation was terminated (pattern 2, n = 10 rats). For pattern 1, increases in ICP during stimulation exhibited a stable plateau without contraction of striated penile muscles, and bilateral transection of the CN eliminated the ICP responses. For pattern 2, increases in ICP observed after stimulation were lower, more variable, and accompanied by significant amplitude variations ("peaks"), caused by contraction of striated penile muscles. Bilateral transection of the CN eliminated the pattern 2 ICP response but did not alter striated muscle contraction. Histological studies documented that pattern 1 and pattern 2 responses occurred via electrical stimulation of the anterior and posterior areas of the MPOA, respectively. Thus both responses appear to result from activation of the CN, but the pattern 2 response apparently involves contraction of the striated penile muscles as well.

The long lasting effects of electrical simulation of the medial preoptic area and medial amygdala on maternal behavior in female rats

A program of repeated electrical (kindling-like) stimulation of the medial preoptic area (MPOA) or the medial amygdala (MedAmyg) on maternal and other behaviors were investigated. Stimulation was applied daily for 14 days (or until a stage 3 motor seizure was observed) using 2 s trains of biphasic square wave pulses at 60 Hz, 1 ms duration and 300–500 μA. Confirmation of afterdischarge using these parametres was established. In the first experiment, maternally experienced (but not post-partum) MedAmyg stimulated animals became maternal more slowly than did MedAmyg not stimulated animals or than MPOA stimulated animals. In the second experiment, virgin animals were used. MPOA stimulation enhanced the female's preference for pup associated environments in the conditioned place preference (CPP) paradigm. MedAmyg stimulation had no effect on CPP performance, but produced a decreased preference for pup odors in a modified hole board test and increased `anxiety' in the open field. These results confirm that the MPOA and the MedAmyg are involved in facilitating and attenuating maternal responsiveness and related (precursor?) behaviors, respectively. It appears that chronic (kindling-like) stimulation of these neural substrates enhances their functions.

Erectile response to hypothalamic stimulation in rats: role of peripheral nerves.

The role of peripheral parasympathetic and sympathetic pathways was explored in erectile responses elicited by hypothalamic medial preoptic area (MPOA) stimulation in adult male anesthetized rats. Under control conditions, MPOA stimulation reliably elicited erectile responses evidenced by an increase of the intracavernous pressure-to-blood pressure ratio. The erectile response was abolished by 1) acute bilateral section of cavernous or pelvic nerves or cauda equina and 2) chronic lesions of pelvic nerves or cauda equina. Acute section of the hypogastric nerve did not significantly decrease the erectile response. The erectile response was significantly depressed after acute or chronic sections of the paravertebral sympathetic chain at the L4-L5 level or chemical sympathectomy with 6-hydroxydopamine. The decrease due to acute sympathetic chain lesion was reversed by bilateral ligation of the external iliac arteries. Accordingly MPOA stimulation elicits erectile responses via 1) activation of the parasympathetic outflow conveyed by the pelvic and cavernous nerves and 2) activation of neural fibers conveyed by the sympathetic pathways. We propose that sympathetic fibers running in the paravertebral sympathetic chain are responsible for vasoconstriction of nonpenile areas to divert blood to the penis, allowing the dramatic increase of penile arterial inflow required for erection.

Stimulation of the medial preoptic area of the hypothalamus in the rat elicits increases in intracavernous pressure

Penile erection can be elicited by various stimuli integrated in the spinal cord and/or higher central nervous structures. The medial preoptic area (MPOA) of the hypothalamus is known to play a key role in the regulation of male sexual behavior. In anesthetized male rats we performed MPOA stimulation via stereotaxically implanted electrodes or canulae delivering l-glutamate. An erectile response, assessed by an increase of intracarvernous pressure (ICP), was recorded during electrical stimulation of the MPOA. Stimulating the posterior region of the MPOA elicited a greater erectile response than stimulation applied to the anterior region. Microinjections of l-glutamate also elicited an ICP increase. Stimulation of MPOA neurons therefore elicits activation of neural pathways controlling penile erection.

Effects of preoptic and hypothalamic lesions in female turkeys during a photoinduced reproductive cycle.

Prolactin (Prl) is released by electrical stimulation in the turkey hypothalamus and preoptic area (POA). Possible trajectories for POA efferents to the median eminence (ME) were tested by placing lesions in the POA, the lateral hypothalamus (LHy), or the ventromedial nucleus of the hypothalamus (VMN) of reproductively quiescent turkey hens, then subjecting them to long photoperiods while monitoring their blood Prl levels and nesting activities. In addition, lesions were made in the VMN of a group of incubating hens to learn whether the lesions would cause the elevated Prl levels to fall or interfere with incubation behavior. Lesions in medial POA, LHy, or VMN prevented the onset of incubation and prevented the large rise in Prl associated with it. However, these lesions did not interfere with the initial, more gradual Prl rise caused by increasing daylengths. Lesions in LHy or VMN appeared to interfere with a pathway lying laterally from POA to ME. Electrical stimulation in medial POA, which caused an increase in circulating Prl, failed to do so in hens with LHy or VMN lesions. Lesions in the VMN of incubating hens caused them to leave the nest and suffer a large decline in Prl, both within 48 h. It is tentatively suggested that incubation behavior and its associated elevated Prl are prevented by the POA lesions and that lesions in LHy or VMN, which mimic POA lesion effects, interfere with POA efferents projecting to ME.

Higher CNS control of penile responses in rats: The effect of hypothalamic stimulation

The effect of electrical stimulation of the medial preoptic area (MPOA) of the hypothalamus on penile responses in rats was investigated. No females were present and penile responses were observed through the use of an inclined mirror. MPOA stimulation was found to elicit two types of penile responses: penile movement within the sheath and protrusion of the penis outside the penile sheath. While these responses also occurred spontaneously during the nonstimulation control sessions, they occurred in significantly higher frequencies following MPOA stimulation. The results also produced an unexpected finding. While studies on the effect of hypothalamic stimulation on copulation show stimulation-bound effects, MPOA stimulation in the absence of a receptive female consistently triggered penile responses as a poststimulation effect.

Electrochemical stimulation of plasma LH and hypothalamic norepinephrine concentrations at short- and long-term intervals after hypothalamic knife cuts

Norepinephrine (NE) concentrations in several diencephalic locations were studied in female rats in conjunction with luteinizing hormone (LH) release after medial preoptic area (MPOA) stimulation at short (7 days) and longer time intervals after surgical interruption of anterior or anterolateral neural connections of mediobasal hypothalamus (MBH). Concentrations of diecephalic NE were altered in two general ways after brain surgery: (1) transient early postoperative increases in some regions which appeared unrelated to the type of surgery performed; and (2) other specific decreases in NE concentration which were related to the types of surgery performed and whether a particular ascending noradrenergic pathway was interrupted. At 180 days after surgery, these two types of change in NE concentrations were no longer present. Maximum increases in plasma LH concentrations observed after electrochemical stimulation of the MPOA at either 7 or 180 days after MBH deafferentation also varied according to: (1) the postoperative interval studied; and (2) the location of pathway interruption. Interruption of anterior MBH pathways showed only a transient (7 day interval) reduction in LH release after MPOA stimulation, whereas when both lateral and anterior pathways were servered, there was a more nearly permanent (180 day interval) disruption of LH release after stimulation. The results of these studies support the contention that anterolateral MBH neural connections may constitute a dynamic neural substrate contributing to a gradual improvement in neuroendocrine function observed after early surgical disconnections.

The interaction of the medial preoptic area and the dorsomedial-ventromedial nuclei of the hypothalamus in the regulation of the mating-induced release of prolactin.

The medial preoptic area (MPOA) and the dorsomedial-ventromedial nuclei (DMN-VMN) of the hypothalamus regulate the mating-induced nocturnal and diurnal surges of prolactin in rats. The neural mechanisms governing the release of the two surges differ. For the nocturnal surge the MPOA serves an inhibitory role while the DMN-VMN serves a stimulatory role. The diurnal surge is controlled by both areas functioning as stimulatory centers. The goal of the present study was to explore the possibility of functional interactions between the MPOA and the DMN-VMN in control of mating-induced prolactin secretion. Stimulation of the MPOA in conscious, cervically stimulated (CS) females suppresses the nocturnal surge of prolactin. To determine if the inhibitory effects of the MPOA operate through the DMN-VMN, electrical stimulation was applied to the MPOA of conscious ovariectomized female rats bearing bilateral electrolytic lesions of the DMN-VMN. In the first experiment, control (sham-stimulated, sham-lesioned) CS females exhibited normal nocturnal surges which peaked at 03.00 h. MPOA stimulation (01.00-05.00 h) of both sham-lesioned and DMN-VMN lesioned CS females inhibited the release of their nocturnal surges. This suggests that the inhibitory function of the MPOA is independent of the DMN-VMN. MPOA stimulation can induce the release of a diurnal surge if the females are anesthetized with pentobarbital. In the second experiment, MPOA stimulation (15.00-19.00 h) of sham-lesioned anesthetized females produced elevated prolactin levels with significant peaks at 15.30 and 19.00 h. Anesthetized females with DMN-VMN lesions did not respond to MPOA stimulation with any change in prolactin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic regulation of mating-induced prolactin release. Effect of electrical stimulation of the medial preoptic area in conscious female rats.

Lesions of the medial preoptic area (MPOA) induce nocturnal prolactin surges similar to those initiated by cervical stimulation (CS). These same lesions can abolish diurnal prolactin surges previously initiated by CS. Based on these results the MPOA has been suggested to contain two functionally dissimilar sets of neurons, one inhibitory for the nocturnal surge and the other stimulatory for the diurnal surge. The present study sought to demonstrate the existence of these neural elements by electrically stimulating the MPOA of conscious ovariectomized female rats during those times of day when these neurons would be most active. Serial blood samples were collected via cannula before, during and after the stimulation. Stimulation of the MPOA (01.00-05.00 h) on day 2 after CS inhibited the nocturnal surge of prolactin while sham MPOA stimulation of CS females did not disturb the nocturnal surge. MPOA stimulation in non-CS females had no effect upon prolactin secretion. Application of MPOA stimulation (15.00-19.00 h) to CS females also suppressed the diurnal surge of prolactin. Sham-stimulated CS females, however, secreted a diurnal surge peaking at 17.00 h. Basal prolactin levels were unaffected by MPOA stimulation (15.00-19.00 h) in non-CS females. The results from these experiments suggest that the MPOA contains neurons inhibitory for both the nocturnal and diurnal prolactin surges. In a further attempt to show a stimulatory role for the MPOA in prolactin regulation, MPOA stimulation was applied (15.00-19.00 h) to pentobarbital anesthetized non-CS females. Pentobarbital treatment allowed the MPOA stimulation to trigger two prolactin peaks, one at 16.00 h and the other at 19.00 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparable surges of luteinizing hormone induced by preoptic or medial basal tuberal electrical stimulation in spontaneously persistent estrous or cyclic proestrous rats.

A previous report demonstrated in cyclic proestrous rats electrically stimulated in the medial preoptic area (MPOA) or the arcuate nucleus-median eminence (ARC/ME) region a close parallel in the progressive increase of serum LH with increasing stimulation time. The present report compares the LH surges induced in middle aged spontaneously persistent estrous (SPE) rats by electrical stimulation of the two regions. Electrical parameters were those previously used. In Series I, MPOA stimulation of SPE rats for 60 min or ARC/ME stimulation for 45 min produced serum LH concentrations 60 and 90 min after stimulation began that were essentially identical to those in proestrous rats similarly treated. In Series II, stimulations were prolonged to 120 min to determine whether LH would continue to rise with the longer stimulation. These rats were all chosen from one shipment and all were born on the same day. Sequential blood samples were taken before stimulation and 60, 90, 120, and 150 min after stimulation began. SPE rats were stimulated in either the MPOA or the ARC/ME and, for comparison, a few proestrous rats that had remained cyclic were stimulated in the MPOA. LH concentrations in these cyclic rats rose more abruptly than in the previous study to amounts significantly higher at both 60 and 90 min, but by 120 min the respective means were not significantly different. In the SPE rats, the 60-min LH levels resembled those in Series I. They continued to rise during the second hour, but only to average levels approximately half those attained in proestrous rats stimulated for 120 min. The comparative increments in MPOA-stimulated and ARC/ME-stimulated rats were similar, although all means in the latter were somewhat higher. The results agree with previous indications that stimulation of either the MPOA or the ARC/ME activates the rostral or caudal portions of a unitary preoptic-tuberal system. Although the tendency of SPE rats to release smaller amounts of LH may result from age-related lowered pituitary responsiveness to LHRH, only future study can determine whether a given degree of preoptic-tuberal stimulation releases equivalent amounts of LHRH in SPE and proestrous rats. Nevertheless, the absence of spontaneous LH surges in SPE points to a primary deficiency in control mechanisms impinging on the preoptic-tuberal system or in its responsiveness thereto.

Amygdala neurones: converging synaptic inputs produced by median eminence and medial preoptic area stimulations in rats.

1. Amygdaloid afferent inputs from the median eminence and the medial preoptic area were studied electrophysiologically in urethane-anaesthetized female rats.2. Stimulation of the surface of the median eminence produced orthodromic responses in about 80% of the forty-seven amygdala units tested and about 65% of the responsive cells showed an excitation.3. Stimulation of the ipsilateral medial preoptic area orthodromically excited seventeen and inhibited twenty of the forty-nine units tested.4. Stimulation of the contralateral medial preoptic area evoked orthodromic excitation in nine and inhibition in three of the twenty-two units tested. These stimuli were ineffective for producing antidromically conducted impulses in the tested units.5. Sixteen of the thirty amygdala units tested for responses to both median eminence and ipsilateral medial preoptic area stimulation responded orthodromically with either excitation or inhibition. The latency of the response to median eminence stimulation was approximately equal to that of the response to ipsilateral preoptic area stimulation in four of these sixteen units.6. A characteristic bursting discharge was observed in eleven amygdala units during and after ipsilateral preoptic area stimulation. A transitory inhibition was evoked simultaneously with the bursting discharge in some units. Seven of the eleven units were also tested for median eminence stimulation, and a transitory excitation was observed in each of these units.7. These results suggest the existence of converging synaptic inputs both from tuberoinfundibular neurones and the ipsilateral medial preoptic area to certain amygdala neurones. They also demonstrate the existence of a specific neural pathway mediating a characteristic self-sustained bursting discharge in some amygdala neurones after such stimulation.

Effects of estradiol-induced lesions of the arcuate nucleus on gonadotropin release in response to preoptic stimulation in the rat.

Female Wistar rats treated with a single subcutaneous injection of 2 mg estradiol valerate (EV) develop gradually progressive, multifocal lesions of the arcuate nucleus. They also exhibit vaginal estrus and endocrine profiles characteristic of animals sustaining anterior hypothalamic deafferentation. In this study, EV-treated females with the arcuate lesions released significantly less LH 1 h following electrochemical stimulation of the medial preoptic area (MPOA) than did normally cycling controls in proestrus. FSH release in response to MPOA stimulation was the same for both groups. As plasma LH concentrations were not significantly different between EV-treated and control animals 1 h after the injection of a potent LHRH analog, the reduced LH response to MPOA stimulation appears to reflect a primarily hypothalamic defect. However, the EV treatment also affected pituitary responsiveness to long-term stimulation as evidenced by reduced LH responses to the LHRH analog after 2 and 3 h. No such differences were seen in the FSH response.

Electrochemically stimulated release of luteinizing hormone and ovulation after surgical interruption of lateral hypothalamic connections in the rat

Plasma LH and FSH were studied in adult female rats following bilateral electrochemical stimulation (ECS) of the medial preoptic area (MPOA). By stereotaxic surgery frontal (FC) and frontal-lateral (LFC) retrochiasmatic "deafferenting" cuts were made with a Halász knife (1.5 mm radius). At 3 and 10 weeks after surgery rats were given pentobarbital (32 mg/kg, i.p.) at 13:30h and stimulated at 15:00h with anodal direct current (20 muA for 60 sec) via concentric bipolar steel electrodes placed bilaterally 0.9 mm from the midline. Stimulation at 3 weeks after FC increased plasma LH from a prestimulation level of 95 +/- ng/ml to 227 +/- 51 ng/ml 80 min after ECS, from which it fell to 111 +/- 29 ng/ml at 160 min, with 2 of 7 animals ovulating the next day. LFC females had similar pre-ECS plasma LH levels 3 weeks after surgery (71 +/- 10 ng/ml), but LH concentrations at 80 min (104 +/- 21 ng/ml) and 160 min post-ECS were significantly lower than those of FC rats, and 0 of 5 rats ovulated. Following a similar protocol 10 weeks after surgery, stimulating the MPOA resulted in comparable elevations in plasma LH and 4 of 10 FC animals ovulated; however, the LFC group still retained a significant blocking effect on ovulation (only 1 of 12 ovulated) when compared with controls the next day. Plasma FSH concentrations were not significantly altered by MPOA stimulation at the parameters employed, either before or after deafferentation. However, LFC resulted in reduced ovarian and uterine weights when compared with controls at both 3 and 10 weeks, whereas FC exerted no observable effect on these organs at these intervals of study. The results of these studies suggest that lateral input to the media basal hypothalamus contributes to MPOA mediated release of LH and ovulation as well as to tonic maintenance of ovarian and uterine function.

Relationship Between Luteinizing Hormone Releasing Hormone Concentration in Hypophysial Portal Blood and Luteinizing Hormone Release in Intact, Castrated, and Electrochemically-Stimulated Rats1

The concentration of luteinizing hormone releasing hormone (LHRH) in hypophysial portal plasma was determined in pentobarbital anesthetized,intact and castrated rats of both sexes, including proestrous rats following electrochemical stimulation of the medial preoptic area (MPOA). Mean LHRH levels in portal plasma obtained between 1400--1700 h from estrous and diestrous rats and from rats ovariectomized for 8 weeks were similar and ranged from 50--55 pg/ml, but the LHRH levels in proestrous rats were less than 12 pg/ml. In addition, hypophysial portal plasma collected during 1100 to 1400 h from animals orchidectomized for 8 weeks and from intact male rats contained mean LHRH concentrations that ranged from 50--65 pg/ml and 30--35 pg/ml, respectively. Electrochemical stimulation of the MPOA in the female rat on the afternoon of proestrus resulted in a marked increase in the concentration of LHRH in portal plasma. LHRH levels in portal plasma during the 0 to 30, 30 to 60, 60 to 90, 90 to 120, and 120 to 150-min periods after electrochemical stimulation of the MPOA were 105 +/- 24.2, 61 +/- 10.8, 51 +/- 8.2, 36 +/- 5.3, and 32 +/- 4.1 pg/ml, respectively. LHRH levels in portal plasma from the unstimulated rats were not detectable (less than 12 pg/ml) in most of the animals. In another group of proestrous rats, the effect of rabbit anti-LHRH serum or normal rabbit serum (NRS) on the release of LH after electrochemical stimulation of MPOA was examined. Pretreatment of proestrous rats with anti-LHRH serum blocked the release of LH due to MPOA stimulation, whereas pretreatment with NRS did not inhibit LH release. On the basis of these findings, it is concluded that electro-chemical stimulation of the MPOA in proestrous rats increases LHRH levels in portal blood and that the enhanced secretion of LHRH stimulates the release of LH from the pituitary gland.

Further studies on sexual differentiation of the brain: response to electrical stimulation in gonadectomized and estrogen primed rats.

Sexual differentiation of the brain was investigated in normal females, neonatally androgenized females and males from the viewpoints of the effects of steroid feedback and the responsiveness to electrical stimulation. Pituitary and serum gonadotropins and prolactin were measured by radioimmunoassay. 1) Pituitary LH in the male was as high as or slightly higher than that in the normal female, but pituitary FSH was much higher in the male than that in the female and pituitary prolactin was much lower in the male than the female. In androgenized females pituitary LH was as low as or slightly lower than that in the normal female, but pituitary prolactin was higher than those in normal cycling females and males. No sex differences were observed in the serum LH and prolactin levels, and serum LH in androgenized females was the same levels in male and female rats. Serum prolactin in androgenized females was higher than that in both normal females and males. Serum FSH in males was higher than that in normal females or in androgenized females. 2) Gonadectomy increased in pituitary and serum LH and FSH in all of normal females, androgenized females and males. Gonadectomy, however, decreased both pituitary and serum prolactin in normal females, but did not change their concentrations in males. In androgenized females pituitary prolactin was reduced by ovariectomy, but not serum prolactin. Estrogen injection into all of gonadectomized animals reduced serum LH and FSH and increased serum prolactin. 3) Electrical stimulation of the medial preoptic area consistently increased serum LH in orchidectomized males and ovariectomized-androgenized females under the estrogen influences. However, stimulation of the medial amygdala did not increase serum LH in orchidectomized males and ovariectomized-androgenized females under the estrogen influences, by contrast, it increased serum LH in the ovariectomized normal females under the same conditions. Hippocampal stimulation increased serum LH slightly in gonadectomized males and androgenized females; by contrast, it decreased serum LH in ovariectomized normal females. 4) In the light-induced constant estrous rats electrical stimulation of both medial preoptic area and medial amygdala increased serum LH, while stimulation of the hippocampus neither increased nor decreased it.Thus, there exists the sexual differentiation of the brain in control of gonadotropin secretion including regulation by the negative and positive feedback influence with gonadal steroids. However, the sexual differentiation of the brain capacity to be involved in the ovulatory release of gonadotropins responding to electrical stimulation appears to be induced by neonatal androgenization in both sexes.