Gonadal Steroid Treatment Research Articles

Differential effects of acute gonadal steroid treatment on neuronal survival in the brainstem following C3 hemicontusion

Following gonadectomy, adult male and female Sprague‐Dawley rats underwent a cervical level 3 hemicontusion spinal cord injury (C3HC SCI) and were randomized to receive testosterone (T), estrogen (E), or sham pellet, and True Blue (TB)‐soaked gelfoam was placed into the lesion cavity to retrogradely label injured supraspinal neurons. At 4 weeks post‐C3HC, brains and cervical spinal cords were removed, sectioned, fixed, mounted, and examined with fluorescence microscopy for TB‐labeled neurons. Neurons in the red nucleus and lateral vestibular nuclei were counted from alternating sections. For the lateral vestibular neurons: sham‐treated males exhibited greater baseline cell survival than did females following injury, T had a positive effect on cell survival in female animals, but E had a negative effect on cell survival in female animals. In the red nucleus, cell survival was similar between the sham‐treated sexes, T did not have an effect on cell survival in females, and E had a negative effect on cell survival in females. The results suggest there are sex differences in the response to injury in different brain stem nuclei, as well as differential and regional effects of T versus E treatments on cell survival. This work was supported by VA Rehab R&D Merit Review Project # B4952I (KJ Jones & JD Houle).Grant Funding Source: VA Rehab R&D Merit Review Project # B4952I (KJ Jones & JD Houle)

Combination of gonadal steroid treatment and peripheral nerve grafting results in a peripheral motoneuron-like pattern of beta II-tubulin mRNA expression in axotomized hamster rubrospinal motoneurons.

Rubrospinal motoneurons (RSMN) represent a population of androgen receptor-containing central motoneurons in rodents. In this study, the ability of testosterone propionate (TP), alone or in conjunction with a peripheral nerve graft (PNG), to alter the molecular program of injured RSMN was accomplished using betaII-tubulin cDNA probes and quantitative in situ hybridization (ISH). Initial fluoro-gold labeling experiments following a T1 hemisection established that, as in the rat, the hamster rubrospinal system is essentially crossed and that injured RSMN concentrate in the ventrolateral region of the red nucleus. In the second experimental series, adult gonadectomized male hamsters were subjected to a right T1 hemisection, with half of the operated animals immediately subcutaneously implanted with 1 10 mm TP Silastic capsule and the other half sham implanted. In a third experimental series, animals were subjected to T1 hemisection, followed by transplantation of a predegenerated autologous segment of peripheral nerve. Half of the animals in each group received TP implants at the time of spinal cord injury and PNG. Postoperative times were 2, 7, and 14 days (dpo). Quantitative ISH was performed using a betaII-tubulin-specific (33)P-labeled cDNA probe, emulsion autoradiography, and computerized image analysis for grain counting. Injury alone resulted in a short-lived increase in betaII-tubulin mRNA expression in the RSMN at 2 dpo, with a significant decline to well below control values at 7 and 14 dpo. TP treatment or PNG alone attenuated, but did not prevent, the down-regulation of betaII-tubulin mRNA. In contrast, the combination of TP with a PNG sustained the injury-induced increase in betaII-tubulin mRNA levels throughout the postoperative period of 2, 7, and 14 dpo. The synergistic effects of the two treatment strategies confirm the importance of targeting multiple aspects of the injury response for therapeutic intervention.

Estrogen receptor (ER)alpha, but not ERbeta, gene is expressed in growth hormone-releasing hormone neurons of the male rat hypothalamus.

GH synthesis and release from pituitary somatotropes is controlled by the opposing actions of the hypothalamic neuropeptides, GH-releasing hormone (GHRH), and somatostatin (SS). There is a striking sex difference in the pattern of GH secretion in rats. Early reports indicate that gonadal steroids have important imprinting effects during the neonatal period. Recently, our laboratory and others have reported that the GH secretory pattern is altered by short-term gonadal steroid treatment in adult rat, suggesting that gonadal steroids are also important determinants of the pattern of GH secretion during adult life. However, the site of action of gonadal steroids in the adult rat hypothalamus is still unknown. In this study, we used in situ hybridization in the adult male rat brain to determine whether GHRH neurons and/or SS neurons coexpress estrogen receptor alpha (ERalpha) and ERss genes. In the medial basal hypothalamus of adult male rat, the ERalpha messenger RNA (mRNA) was located in medial preoptic area (MPA) and arcuate nucleus (ARC), whereas ERss mRNA was detected in MPA, supraoptic nucleus, and paraventricular nucleus. From studies using adjacent sections, the distribution of ERalpha mRNA-containing cells appeared to overlap in part with those of GHRH and SS expressing cells only in the ARC. On the other hand, the distribution of ERss mRNA-containing cells does not appear to overlap with GHRH cells or SS cells. The double label in situ hybridization studies showed that in the ARC, 70% of GHRH neurons contain ERalpha mRNA, whereas less than 5% of SS neurons expressed the ERalpha gene. These results indicated that GHRH neurons are direct target cells for estrogens, and estrogens may act directly on GHRH neurons through ERalpha during adult life to modify GH secretory patterns.

Estrogen Receptor (ER) , But Not ER , Gene Is Expressed in Growth Hormone-Releasing Hormone Neurons of the Male Rat Hypothalamus

GH synthesis and release from pituitary somatotropes is controlled by the opposing actions of the hypothalamic neuropeptides, GH-releasing hormone (GHRH), and somatostatin (SS). There is a striking sex difference in the pattern of GH secretion in rats. Early reports indicate that gonadal steroids have important imprinting effects during the neonatal period. Recently, our laboratory and others have reported that the GH secretory pattern is altered by short-term gonadal steroid treatment in adult rat, suggesting that gonadal steroids are also important determinants of the pattern of GH secretion during adult life. However, the site of action of gonadal steroids in the adult rat hypothalamus is still unknown. In this study, we used in situ hybridization in the adult male rat brain to determine whether GHRH neurons and/or SS neurons coexpress estrogen receptor α (ERα) and ERβ genes. In the medial basal hypothalamus of adult male rat, the ERα messenger RNA (mRNA) was located in medial preoptic area (MPA) and arcuate nucleus (ARC), whereas ERβ mRNA was detected in MPA, supraoptic nucleus, and paraventricular nucleus. From studies using adjacent sections, the distribution of ERα mRNA-containing cells appeared to overlap in part with those of GHRH and SS expressing cells only in the ARC. On the other hand, the distribution of ERβ mRNA-containing cells does not appear to overlap with GHRH cells or SS cells. The double label in situ hybridization studies showed that in the ARC, 70% of GHRH neurons contain ERα mRNA, whereas less than 5% of SS neurons expressed the ERα gene. These results indicated that GHRH neurons are direct target cells for estrogens, and estrogens may act directly on GHRH neurons through ERα during adult life to modify GH secretory patterns.

Brain Vasotocin Pathways and the Control of Sexual Behaviors in the Bullfrog

The neurohypophysial peptide arginine vasotocin (AVT) alters the display of several sexually dimorphic behaviors in the bullfrog (Rana catesbeiana). These behaviors include mate calling, release calling, call phonotaxis, and locomotor activity. Populations of AVT-immunoreactive cells are present in six areas of bullfrog brain and fibers are widespread. Neural areas involved in vocalization, in particular, contain AVT cells and fibers. As well, AVT concentrations in a subset of brain areas are sexually dimorphic and steroid sensitive. Effects of gonadectomy and gonadal steroid treatment vary, depending on the brain area and sex of the frog. For example, some anterior areas are sensitive to changes in both dihydrotestosterone (DHT) and estradiol. In some posterior brain areas, on the other hand, AVT levels are affected only by DHT. A similar situation exists for putative AVT receptors in bullfrogs. Receptors are widespread, occurring in many areas that have been linked to behavior. Receptor concentrations are sexually dimorphic in the amygdala pars lateralis, hypothalamus, pretrigeminal nucleus, and dorsolateral nucleus. Estradiol alters AVT receptor level in the amygdala of both sexes of bullfrog and both estradiol and DHT alter the receptor number in the pretrigeminal nucleus, but only in males. The mechanisms responsible for steroid effects on vasotocin neurons and their targets are unknown. Specific AVT cells, fiber terminal fields, and receptor populations are likely influenced by gonadal steroids for effective timing of individual behaviors displayed by bullfrogs.

Renal oxytocin receptor messenger ribonucleic acid: characterization and regulation during pregnancy and in response to ovarian steroid treatment.

Although the neurohypophyseal hormone oxytocin (OT) is best know for its role in reproduction, OT also stimulates natriuresis at physiological plasma levels. This effect is mediated via specific renal OT receptors (OTRs). In the present study, we have characterized rat renal OTR gene transcripts and assessed their regulation during gestation and in response to gonadal steroid treatment. Using a specific rat OTR probe, two major OTR messenger RNA (mRNA) bands [6.7 and 4.8 kilobases (kb)] were detected in renal extracts, corresponding to two of the three bands present in rat uterus. In contrast to the dramatic rise of OTR mRNA levels at term in the uterus and pituitary, renal OTR mRNA levels underwent a strong more than 3-fold decrease at term. Binding studies using a iodinated specific OT antagonist revealed a concomitant decrease in renal OT-binding sites. On the other hand, estrogen (E2) treatment led to an increase in renal OTR mRNA levels, as is also the case in the uterus and pituitary. However, the predominant E2-induced mRNA species were shorter (3.6 and 3.2 kb) than those present in control rat kidneys (6.7 and 4.8 kb). Analysis by reverse transcriptase-PCR and 5'- and 3'-directed complementary DNA probes indicated that the E2-induced OTR mRNA transcripts possessed the same coding region, but contained a shortened 3'-untranslated region. Binding studies showed that E2 treatment also led to an increase in renal OT-binding sites, suggesting that the shortened OTR transcripts encoded a functional receptor. The present study indicates that the uterine-type OTR gene is expressed in rat kidneys, but that the mechanisms controlling the expression of this gene in the two tissues are markedly different. The differential tissue-specific regulation of OTR gene expression may represent a mechanism by which circulating OT can assume a multifunctional role in both reproduction and sodium homeostasis.

Oxytocin receptor gene expression in the rat uterus during pregnancy and the estrous cycle and in response to gonadal steroid treatment

It is well established that uterine oxytocin receptors (OTRs) are strongly up-regulated immediately before parturition as well as in response to estrogen (E2) administration. Progesterone (P4), on the other hand, induces a rapid down-regulation. We recently cloned the rat OTR gene and characterized its expression in the rat uterus. In this study, we examined the regulation of OTR messenger RNA (mRNA) levels in rat uterus during pregnancy, the estrous cycle, and in response to gonadal steroid treatment. OTR mRNA levels increased more than 25-fold during gestation: 4.5-fold during the first 21 days and 6-fold within 24 h between day 21 and the onset of parturition. Uterine OTR mRNA levels fell rapidly by 85% within 24 h following parturition. By in situ hybridization, OTR mRNA was localized specifically to the longitudinal and circular layers of the myometrium but was not detected in the endometrium. During the estrous cycle, OTR mRNA levels increased 2-fold between metestrus and proestrus, whereas oxytocin (OT) binding rose more than 10-fold within this same interval. Treatment of ovariectomized rats with E2 lead to a significant increase in both OTR mRNA levels (4.4-fold) and OT binding (< 6-fold). Cotreatment with P4 strongly reduced OT binding by 75% (P < 0.01) but did not significantly affect the E2-induced rise in OTR mRNA (11% decrease, P > 0.1). Our data suggest that the increased expression of OT binding sites observed at the onset of labor and at proestrus is mediated, at least in part, by an E2-induced up-regulation of OTR gene expression. However, it also appears that OTR mRNA levels are not the sole determinants of uterine OT binding. Specifically, P4-mediated OTR down-regulation cannot be explained by an effect on OTR mRNA accumulation and may involve novel mechanisms acting at translational or posttranslational levels.

Oxytocin receptor gene expression in the rat uterus during pregnancy and the estrous cycle and in response to gonadal steroid treatment.

It is well established that uterine oxytocin receptors (OTRs) are strongly up-regulated immediately before parturition as well as in response to estrogen (E2) administration. Progesterone (P4), on the other hand, induces a rapid down-regulation. We recently cloned the rat OTR gene and characterized its expression in the rat uterus. In this study, we examined the regulation of OTR messenger RNA (mRNA) levels in rat uterus during pregnancy, the estrous cycle, and in response to gonadal steroid treatment. OTR mRNA levels increased more than 25-fold during gestation: 4.5-fold during the first 21 days and 6-fold within 24 h between day 21 and the onset of parturition. Uterine OTR mRNA levels fell rapidly by 85% within 24 h following parturition. By in situ hybridization, OTR mRNA was localized specifically to the longitudinal and circular layers of the myometrium but was not detected in the endometrium. During the estrous cycle, OTR mRNA levels increased 2-fold between metestrus and proestrus, whereas oxytocin (OT) binding rose more than 10-fold within this same interval. Treatment of ovariectomized rats with E2 lead to a significant increase in both OTR mRNA levels (4.4-fold) and OT binding (< 6-fold). Cotreatment with P4 strongly reduced OT binding by 75% (P < 0.01) but did not significantly affect the E2-induced rise in OTR mRNA (11% decrease, P > 0.1). Our data suggest that the increased expression of OT binding sites observed at the onset of labor and at proestrus is mediated, at least in part, by an E2-induced up-regulation of OTR gene expression. However, it also appears that OTR mRNA levels are not the sole determinants of uterine OT binding. Specifically, P4-mediated OTR down-regulation cannot be explained by an effect on OTR mRNA accumulation and may involve novel mechanisms acting at translational or posttranslational levels.

Regulation of rat luteinizing hormone beta gene expression in transgenic mice by steroids and a gonadotropin-releasing hormone antagonist.

Transcriptional regulation of the rat LH beta (rLH beta) gene was studied through the use of transgenic mice bearing a region of the rLH beta gene (from -2 kb to +41 bp) linked to a luciferase (LUC) reporter gene. All 7 founder mice were successfully bred with B6SJLF1 mates and exhibited germ line transmission of the LH beta LUC transgene. Levels of rLH beta LUC activity were highest in the pituitary, but activity was also detected in ovary, testis, and hypothalamus. Pituitary rLH beta LUC activity was found to be regulated by gender, gonadectomy, gonadal steroid replacement, and GnRH antagonist administration. Females had higher basal pituitary rLH beta LUC activity than males. This activity was increased 2- to 4-fold seven days postovariectomy, and stimulated activity was suppressed to intact levels by daily injections of 17 beta estradiol (E2; 300 ng). In males, castration increased pituitary LUC activity 2- to 4-fold, and this suppressed to intact levels by daily injections of 25 micrograms dihydrotestosterone (DHT). The postgonadectomy rise in pituitary rLH beta LUC activity in females and males was blocked by daily administration of the GnRH antagonist Antide (60 micrograms), which also suppressed serum LH and LH beta mRNA levels to a similar extent. Rat LH beta LUC activity measured in the hypothalamus was not altered by gonadectomy or gonadal steroid or Antide treatment, demonstrating that this regulation is pituitary-specific. These results indicate that feedback regulation of pituitary rLH beta LUC gene expression is operational in this transgenic mouse model.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum hormones in response to estradiol and (OR) progesterone in ovariectomized cows after thyroidectomy

To evaluate the effect of gonadal steroid treatment and thyroidectomy on concentrations of gonadotropins and thyroid-stimulating hormone in the bovine, nonlactating Holstein cows were either thyroidectomized and ovariectomized (THYOVEX; n=6) or ovariectomized only (OVEX; n=4), and subsequently treated with no gonadal steroids (control), estradiol-17β (E 2), progesterone (P 4), or P 4+E 2 in a 2 × 4 factorial experiment. Averaged across steroid treatments, baseline concentrations of luteinizing hormone (LH; P < .05) and follicle-stimulating hormone (FSH; P <.10) were higher in THYOVEX cows than in OVEX cows. Pulse frequencies and amplitudes of LH and FSH did not differ between THYOVEX and OVEX cows. Secretion of TSH was pulsatile and all concentrations and pulsatile characteristics of TSH were increased (P < .05) in THYOVEX compared to OVEX cows. Treatment with E 2 and P 4 decreased (P < .05) baseline concentrations and magnitude of LH pulses, whereas P 4+E 2 increased (P < .01) pulse frequency of LH and FSH. Amplitude of LH and FSH pulses were not affected by treatment with either steroid. Treatment with P 4+E 2 decreased (P < .05) baseline concentrations of TSH, whereas pulse frequency, and magnitude and amplitude of TSH pulses were not altered by treatment with steroids. Mean concentrations of LH and FSH were similar during 48 hr after termination of E 2 and P 4+E 2 treatments, but concentrations of TSH were higher (P = .06) after P 4+E 2 than after E 2. Secretion of TSH showed a diurnal variation, with the lowest concentrations in the morning and highest in the afternoon. These results indicate that thyroidectomy influenced secretion of gonadotropins in OVEX cows.

A Modulatory Role for Luteinizing Hormone-Releasing Hormone in Nociceptive Responses of Female Rats

We have shown that responsiveness to noxious stimuli change after gonadal steroid treatment and during the estrous cycle. In the present study, we evaluate the role of LHRH in modulating nociceptive responses in female rats. In ovariectomized (OVX) rats, an LHRH agonist ([ Des-Gly10] LHRH ethyl amide; 1 ng/rat/microliters), given intraventricularly (icv) at either 90, 60, or 30 min before a hot-plate test caused a time-dependent, significant increase in sensitivity to the noxious thermal stimulus (hyperalgesia) vs. saline-treated controls. Further, the LHRH agonist (1 ng/rat/microliters; icv) attenuated morphine (5 mg/kg, sc)-induced antinociception. The injection of an LHRH antagonist, [D-Phe2,Pro3,D-Phe6] LHRH, to OVX rats in doses of 0.1, 1, or 10 ng/rat 30 min prior to morphine, enhanced and prolonged morphine-induced antinociception in a dose-dependent manner. Moreover, the hyperalgesia observed in OVX rats treated with naloxone (1 mg/kg, sc) was reversed by preinjection of either the LHRH antagonist (0.1 ng/rat, icv) or LHRH antiserum. OVX rats primed with estradiol benzoate (EB) and progesterone (P) were less sensitive to the antinociceptive effect of morphine than OVX rats. When EBP-treated rats received the LHRH antagonist prior to morphine, a twofold increase in morphine-induced antinociception was observed. A similar effect was observed in EBP-treated rats after the injection of LHRH antiserum. In conclusion, LHRH may interact with central opioid systems causing an increased sensitivity to nociceptive stimulation (hyperalgesia) and reduction of the antinociceptive effect of morphine.

Differential responses of hypothalamic LHRH-I and -II to castration and gonadal steroid or tamoxifen treatment in cockerels

Changes in the hypothalamic contents of LHRH-I and LHRH-II were determined in intact and castrated cockerels injected i.m. with gonadal steroids or tamoxifen. An increase in the plasma concentration of LH after castration was accompained by a significant increase in the content of LHRH-I in the posterior hypothalamus (including the mediobasal hypothalamus and median eminence) which was reversed by oestradiol benzoate given on days 14 and 15 after castration. Under similar circumstances, testosterone propionate did not modify the hypothalamic content of LHRH-I, even though both steroids reduced the plasma concentrations of LH to levels below those of intact cockerels. Treatment of intact cockerels with oestradiol benzoate significantly increased the content of LHRH-I in the posterior hypothalamus, whilst testosterone propionate was again without effect. Tamoxifen significantly raised the plasma concentration of LH in intact cockerels and partially antagonized the suppressive effect of oestradiol benzoate and testosterone on LH secretion in castrated cockerels. However, an anti-oestrogenic effect of tamoxifen on the hypothalamic content of LHRH-I was not demonstrated. There was no evidence of any changes in the hypothalamic content of LHRH-II after castration, with or without gonadal steroid replacement. A change in the hypothalamic content of LHRH-I in response to manipulation of the steroid environment would imply an involvement of this peptide in the mechanism by which gonadal steroids regulate the release of LH. The absence of changes in the hypothalamic content of LHRH-II in the same circumstances suggest that it is not directly involved in the control of LH secretion by the gonadal steroid negative feedback loop.

Gonadal steroid and chronic morphine treatment do not change the posttranslational processing of β-endorphin in the rat brain

The present study examines whether two treatments known to induce refractoriness to exogenous morphine produce this desensitization through a change in the posttranslational processing of brain β-endorphin (β-End). The first experiment examined whether an ovarian steroid regimen which produces a transient desensitization of brain opiate receptor mechanisms alters β-End processing in the preoptic area (POA), medial basal hypothalamus (MBH), and brainstem (BS). The second experiment monitored the effects of morphine pellet treatment, known to produce morphine dependency, on immunoreactive β-End forms in the hypothalamus and periaquaductal gray area of the midbrain (PAG). The individual molecular forms of β-End were separated using ion exchange chromatography and collection fractions were quantitated for β-End immunoreactivity by RIA. The results show that regional differences occur in the posttranslational processing of β-End. In the hypothalamus, MBH and POA, β-End-(1–31) and its non-acetylated C- terminal cleavage products, β-End-(1–27) and β-End-(1–16) were the predominant forms of β-End. The PAG pools produced a β-End peptide elution profile similar to the hypothalamus, although small amounts of N-acetyl-β-End-(1–31) were also identified. The BS exhibited the least posttranslational processing of β-End; β-End-(1–31) was the primary product with smaller amounts of β-End-(1–27) and β-End-(1–26) observed. However, neither ovarian steroid treatment nor chronic morphine produced any changes in posttranslational processing of β-End or in total β-End concentration in any of the brain regions examined in these experiments. These data indicate that the refractoriness or tolerance to exogenous morphine associated with steroid or chronic morphine treatment cannot be explained by alterations in the biological activity of β-End resulting from the differential regulation of its posttranslational processing products.

Administration of gonadal steroids to neonatal rats affects beta-endorphin levels in the adult

Administration of gonadal steroids to neonatal rats has a profound effect on the function of the neuroendocrine system in the adult animal. Considering that gonadal steroids modulate hypothalamic and pituitary levels of beta-endorphin (BE) in adult male and female rats, the effects of neonatal gonadal steroid treatment on BE levels in the adult animal were investigated. Neonatal male rats were administered testosterone and neonatal female rats were treated with estrogen. Matched control littermates received vehicle. All animals were sacrificed at 90 days of age. Neonatal gonadal steroid treatment did not affect the level of immunoreactive beta-endorphin (IR-BE) in the anterior pituitary (AP) of male rats but did result in a significant increase in IR-BE in the AP of female rats. Neonatal administration of gonadal steroids produced a significant decrease in IR-BE in the neurointermediate lobe of the pituitary (NIL) of both male and female rats, with the magnitude of the decrease being greater in the NIL of the female rats. IR-BE levels in the hypothalamus of male or female rats were not altered by the treatments. Column chromatography indicated that the increase in IR-BE in the AP represented a proportional increase in BE and beta-lipotropin, while the reduction in IR-BE in the NIL of the treated rats represented a reduction in BE. These findings suggest that gonadal steroids may influence the development of the neurotransmitter systems which regulate BE levels in the adult pituitary, the development of the biosynthetic mechanisms of the adult pituitary, or both.

Long-term weekly gonadal steroid treatment: effects on plasma prolactin, sexual behavior and hypothalamic-preoptic area catecholamines.

Treatment of intact female rats with weekly injections of estradiol benzoate followed 48 h later by progesterone reliably induced high levels of sexual behavior. After 15-20 treatments, 25% of one group of females became refractory to the sexual-activity-inducing effects of ovarian steroids. The apparent deficit in sexual behavior could not be attributed to variation in prolactin secretion, as long-term steroid treatment resulted in greatly elevated circulating prolactin levels (greater than 1 microgram/ml) which were equivalent in good sexual responders (lordosis quotient, LQ greater than or equal to 90) and sexually refractory females (LQ less than or equal to 20). In control rats, short-term steroid treatment (5 weeks) decreased dopamine (DA) and dihydroxyphenylacetic acid (Dopac) concentrations in the median eminence (ME) and induced good sexual behavior. Interestingly, a similar pattern of decreases in DA and Dopac levels of ME was observed in those long-term-treated rats displaying good sexual behavior but not in the sexually refractory females. Further, a significant increase in DA concentration in the preoptic-anterior hypothalamic area of the sexually refractory females was observed. These data are interpreted to suggest that severe and chronic elevations in circulating levels of prolactin, induced by chronic ovarian steroid treatment, are not universally associated with a disruption of sexual behavior and increased dopaminergic function in the ME, seen in females with normal sexual behavior, was conspicuously absent in female rats that became refractory to the sexual-behavior-inducing effects of ovarian steroids.

Differential effects of flurothyl- and electro-convulsive shock on sexual maturation and prolactin release in the rat

The effects of single and repeated seizures on luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin secretion and on the onset of sexual maturation in rats are described. In addition, the influence of convulsions generated electrically (electroconvulsive shock, ECS) and chemically (using flurothyl) are compared. Repeated flurothyl convulsions and ECS (one daily convulsion from age 24 days) significantly delay vaginal opening in female rats. The incidence of first ovulation at maturation is reduced to 20% compared with 70-100% for untreated groups. Body and adrenal weights in immature rats are not modified by flurothyl convulsions. Repeated ECS does not influence adrenal weight although somatic growth is inhibited. In an effort to clarify the mechanism of action of convulsions on puberty onset, we examined acute changes in LH, FSH and prolactin secretion and the surge response of LH/FSH to gonadal steroid priming. A single flurothyl convulsion potently inhibits prolactin secretion. In contrast, an ECS acutely stimulates prolactin release in male and female rats. Convulsive seizures do not consistently alter tonic gonadotropin output. However, both flurothyl convulsions and ECS attenuate estradiol benzoate/progesterone-induced LH and FSH surges in ovariectomized rats though this is apparently not mediated by dopamine/prolactin since bromocriptine treatment delays sexual maturation without preventing ovulation at first estrus. Similarly, bromocriptine does not disrupt LH/FSH surges induced by gonadal steroid treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of monoamine oxidase inhibition on female sexual behavior, serotonin levels and type A and B monoamine oxidase activity.

Administration of various monoamine oxidase (MAO) inhibitors to ovariectomized-adrenalectomized, estrogen and progesterone-treated female rats was utilized to study possible relationships between the lordosis response and levels of preoptic-hypothalamic MAO and serotonin (5HT). Depending on the drug and dose, behavioral changes ranged from no effect to complete abolition of the lordosis response. Surprisingly, only those treatments which substantially inhibited both the A and B forms of MAO affected lordosis. However, behavioral deficits were related to increases in 5HT levels in a graded manner. In fact, a sigmoid-shaped dose-response curve was generated by plotting either the lordosis quotient or quality score versus the percent increase in preoptic-hypothalamic 5HT. Proceptivity was reduced by some treatments but not abolished, suggesting that different neurotransmitters may mediate receptive and proceptive components of female sexual behavior. In general, these results support the hypothesis that 5HT may exert inhibitory control over hormone dependent female sexual behavior and suggest that previously reported changes in MAO activity and 5HT levels following gonadal steroid treatment could pay a role in hormonal facilitation of female sexual behavior.

Constancy of adult hypothalamic tyrosine hydroxylase after gonadal steroid treatment during development.

Tyrosine hydroxylase (TH) was studied in the entire hypothalamus of 60-day-old male and female rats, and its activity was similar in both sexes. Administration of estrogen or androgen to male or female pups soon after birth and during development did not affect the kinetic parameters of TH. It is, thus, suggested that sexual dimorphism in the levels and turnover of catecholamines (CA) and their sensitivity to fluctuations in gonadal steroids during development do not depend on corresponding sex-related or steroid-sensitive differences in the synthesis of hypothalamic CA.

Differential effects of low serum levels of estradiol-17 beta on hypothalamic LHRH levels and LH secretion in castrated male rats.

In castrated male rats, gonadal steroid treatment raises the medial basal hypothalamic (MBH) LHRH levels and suppresses LH release. We have now examined whether the steroid-induced MBH LHRH response could occur concomitantly with normal pituitary LH secretion. Of the various concentrations tested, serum estradiol-17 beta (E2) levels in the range of 9-16 pg/ml consistently and selectively stimulated the accumulation of LHRH in the MBH after a long latency period of 60-72 h. These low E2 levels did not suppress LH release at any time interval. Serum LH levels and the episodic pattern of LH secretion were similar to those of castrated control rats. It is unlikely that enhanced pituitary sensitivity in E2-treated rats may have compensated for a decrease in LHRH release since the LH response to exogenous LHRH was similar in E2-treated and control rats. These studies show that dissociation of the feedback effects on the MBH LHRH and pituitary gland LH release may be obtained with low serum concentrations of E2 in male rats; low E2 levels stimulate LHRH accumulation in the MBH by mechanisms which may not involve inhibition of LHRH release.

Sex and hormonal modification of 6-keto-PGF 1α release by rat aorta

The stable breakdown product of prostacyclin, 6-keto-PGF 1α, was estimated in plasma samples after incubation with rat aortic rings. The 6-keto-PGF 1α concentration obtained with the male aortae was two-fold higher than that of the female. Ovariectomy markedly increased 6-keto-PGF 1α six-fold, but castration had no effect. Estradiol and progesterone treatment of the ovariectomized female suppressed (by 50%) and enhanced (two-fold) 6-keto-PGF 1α. Testosterone was without effect in gonadectomized males and females. Castrate males did not respond to gonadal steroid treatment.