beta-EP Levels Research Articles

Effects of repeated electroacupuncture on β-endorphin and adrencorticotropic hormone levels in the hypothalamus and pituitary in rats with chronic pain and ovariectomy

To explore the mechanism of electroacupuncture (EA)-induced cumulative analgesic effects on chronic pain in rats with or without ovariectomy (OVX). A total of 110 female Wistar rats were randomized into normal control (n=10), chronic constrictive injury (CCI, n=10), CCI+EA (n=30), OVX+CCI (n=30), and OVX+CCI+EA (n=30) groups. Each of the latter 3 groups was further divided into 2 days (2 d), 2 weeks (2 W) and 3 weeks (3 W) subgroups, respectively (n=10 in each subgroup). The CCI pain model was established by ligature of the right sciatic nerve, and the memory impairment model duplicated by OVX. The paw withdrawal latency (PWL, pain threshold) of the bilateral footplates was detected by radiant heat irradiation, and the bilateral difference in PWL (PWLD) was used to evaluate changes in the pain reaction. Morris water maze test was conducted for evaluating the rats' learning-memory ability. EA was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) for 2 d, 2 W and 3 W, respectively. Pituitary and hypothalamic beta-endorphin (EP) and adrenocorticotrophic hormone (ACTH) contents were detected by immunoradioassay. Compared with the CCI group, PWLD of the CCI+EA-3 W group decreased significantly (P<0.05). Compared with the OVX+CCI group, PWLD of the OVX+CCI+EA-3 W group was lowered considerably (P<0.05), but the value was markedly higher than its basal value and those of the normal control and CCI+EA groups (P<0.05). In comparison with the sham-OVX group, the escape latency, swimming distance (SD) in the target quadrant and total SD were increased remarkably in the OVX group (P<0.05), while the number of target platform crossings was decreased significantly (P<0.05), suggesting an impairment of the OVX rats' learning-memory ability. In simple CCI rats, both beta-EP and ACTH contents of the pituitary increased markedly (P<0.05), and those of the hypothalamus decreased obviously compared to the normal control group (P<0.05). After EA, pituitary and hypothalamic ACTH levels were significantly lowered at 2 d and hypothalamic ACTH and beta-EP contents increased obviously at 3 W in comparison with the CCI group (P<0.05). In OVX+CCI rats, following EA, pituitary beta-EP contents at 2 d, 2 W and 3 W, and hypothalamic beta-EP and ACTH contents at 2 W and hypothalamic ACTH levels at 3 W increased significantly (P<0.05), but hypothalamic beta-EP level at 3W decreased markedly (P<0.05). The effects of repeated EA in lowering pituitary ACTH and raising hypothalamic beta-EP and ACTH levels disappeared after OVX+CCI. Repeated EA has a cumulative analgesic effect, which is closely associated with its effects in regulating pituitary and hypothalamic beta-EP and ACTH levels. OVX may weaken the analgesic effect of EA by affecting hypothalamic-pituitary axis activity.

Effects of patient-controlled analgesia with small dose ketamine combined with morphine and the influence thereof on plasma beta-endorphin level in patients after radical operation for esophageal carcinoma

To evaluate the effects of patient-controlled analgesia (PCA) with small dose ketamine combined with morphine on analgesia and influence thereof on the plasma beta-endorphin (EP) level in the patients after radical operation for esophageal carcinoma. Thirty ASAI-II patients, aged 35-65, weighing 42-75 kg, with visual analogue score>or=3, undergoing elective radical operation for esophageal carcinoma under general anesthesia received intravenous morphine 2 - 3 mg were randomly divided into 2 equal groups: group m receiving morphine 0.02 mg.kg(-1).h(-1), and with group mk receiving morphine 0.02 mg.kg(-1).h(-1) combined with ketamine 0.08 mg.kg(-1).h(-1) for 50 h. In the course of treatment the patients received intravenous injection of morphine 2-3 mg when the VAS was >or=3. VAS was recorded 4, 8, 20, 24, and 48 h after operation. The amount of morphine used after operation, PCA button pressing times (effective/active), side effects, and vital signs including pulse, saturation of blood oxygen, respiratory rate, heart rate, and average arterial pressure were recorded. Central venous blood samples were collected when entering the operation room (T0), by the end of operation (T1), and 6 h (T2), 24 h (T3), and 48 h (T4) after operation respectively to examine the beta-endorphin level. During the period 4-48 h after operation the VAS scores of the group mk were significantly lower than those of the group m in activity state (all P<0.05) and were not significantly different those of the group m at resting state (all P>0.05). The total amount of morphine consumed and the actual PCA button pressing times were significantly less in the group mk than in the group m (both P<0.05). The incidence rates of nausea, vomiting, and pruritus of the group mk were all significantly lower than those of the group m (all P<0.05). There were not significant differences in the incidence rates of dreaming and pseudoesthesia between these 2 groups. All the vital signs were stable in the 2 groups. The plasma beta-EP levels at the time point T1 of these 2 groups were both significantly higher than those at T0 (both P<0.05). The plasma beta-endorphin levels at T2-4 of the group mk decreased gradually from the level at T1 to the level at T0, and the plasma beta-endorphin levels of the group m rapidly decreased from the level at T0 to the T0 level and remained at this level to the 48 h after operation. The combination of small dose of ketamine with morphine provides optimal analgesia with low side-effect rate and little effect on the plasma beta-EP level.

Time-Dependent Neuroendocrine Alterations and Drug Craving during the First Month of Abstinence in Heroin Addicts

Rationale: Heroin use and withdrawal cause abnormality in the endocrine system. However, the time course of neuroendocrine alterations in heroin addicts during pharmacologically unassisted withdrawal is still unclear. Objectives: To investigate alterations in cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-EP), leptin, and neuropeptide Y (NPY) during the first month of abstinence in heroin addicts. Methods: Twelve heroin addicts and eight matched healthy control subjects were recruited for this study. The neuroendocrine alterations and self-reported heroin craving, anxiety, and depression in heroin addicts were assessed at different time points (days 3, 10, and 30) of first month of abstinence from heroin use. Results: Self-reported heroin craving, anxiety, and depression in heroin addicts decreased gradually during the first month of abstinence. The cortisol levels increased from abstinence day 3 to 30, while ACTH and beta-EP levels decreased over this period in heroin addicts. The leptin and NPY levels were significantly decreased on days 3 and 10 but had normalized on day 30 of abstinence. A positive correlation between cortisol level and heroin craving, anxiety, and depression was observed, while a negative correlation was observed between beta-EP level and craving and anxiety and between leptin and depression and NPY and anxiety. Conclusions: Abnormal alterations in the neuroendocrine system, including levels of cortisol, ACTH and beta-EP persist throughout the first month of abstinence. These results suggest that neuroendocrine system dysfunctions in heroin abusers is independent of the acute and protracted withdrawal syndromes, and may thus contribute to relapse to heroin use.

Cerebrospinal Fluid Rett Syndrome β-Endorphin

An hypothesis of increased endorphinergic activity has been proposed to account for the characteristic symptoms of Rett syndrome. Cerebrospinal fluid samples from eight girls with Rett syndrome were analysed for beta-endorphin (beta-EP) immunoactivity and compared with samples from a control group of 15 children with acute leukaemia in remission. Severity of symptoms was not found to be related to beta-EP level. A group of early-treated adolescents with phenylketonuria had beta-EP levels similar to the Rett syndrome patients, but no symptoms resembling theirs. Therefore it is unlikely that increased levels of beta-EP are of primary pathogenetic significance. The conflicting findings of many earlier reports may be a result of differences between control groups.

Effect of tibolone administration on central and peripheral levels of allopregnanolone and β-endorphin in female rats

We evaluated the effects of tibolone oral administration on neuroendocrine function by investigating the modulation exerted by tibolone administration on allopregnanolone and central and peripheral beta-endorphin (beta-EP) levels in ovariectomized rats. Female Wistar rats (N = 64) were included: 48 rats were ovariectomized, 8 cycling rats were included as controls, and 8 cycling rats were treated with placebo. The ovariectomized animals were divided into six groups: untreated rats and those that received 14-day oral treatment with either placebo, estradiol valerate (E2V) 0.05 mg/kg/d, or tibolone (0.1, 0.5, or 2 mg/kg/d. beta-EP levels were assessed in the frontal lobe, parietal lobe, hippocampus, hypothalamus, anterior pituitary, neurointermediate pituitary, and plasma, whereas allopregnanolone levels were measured in the frontal lobe, parietal lobe, hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum. The administration of tibolone (0.5 and 2 mg/kg/d) in ovariectomized rats induces a significant increase of allopregnanolone in the frontal lobe, parietal lobe, hippocampus, hypothalamus, whereas in serum a significant increase of allopregnanolone occurs only with the dose of 2 mg/kg/d, a significant decrease in allopregnanolone levels occurs in the adrenal glands. No changes occurred in the anterior pituitary. Tibolone doses of 0.5 and 2 mg/kg/d induced a significant increase in beta-EP content in the frontal lobe, hypothalamus, and neurointermediate lobe; and, at doses of 2 mg/kg/d, in the parietal lobe, anterior pituitary, and plasma, without changes in the hippocampus. Compared with E2V, 0.5 mg/kg/d tibolone showed a similar effect on allopregnanolone and beta-EP in most brain regions. Tibolone administration affects beta-EP and allopregnanolone levels, playing a role as a neuroendocrine modulator.

Ultrasonic interventional analgesia in pancreatic carcinoma with chemical destruction of celiac ganglion

To detect the therapeutic effects of chemical destruction of celiac ganglion in patients with pancreatic carcinoma with intractable pain. Ninety-seven cases with advanced pancreatic carcinoma received chemical destruction of celiac ganglion-5 mL pure alcohol injection around celiac artery under ultrasonic guidance. The changes of visual analogue scale (VAS), serum substance P (Sub P), beta-endopeptide (beta-EP) and T-lymphocyte subtypes level were compared between pre- and post-therapy. Successful rate of puncture was 98.7%, with one failure. No serious complications such as traumatic pancreatitis, pancreatic fistula, abdominal cavity hemorrhage or peritoneal infection occurred. VAS, serum Sub P and beta-EP level significantly changed after treatment (8.0+/-2.3 vs 4.6+/-2.1, 254.1+/-96.7 vs 182.4+/-77.6, 3.2+/-0.8 vs 8.8+/-2.1, P<0.01, P<0.05, P<0.01) with complete relief rate 54.2%, partial relief rate 21.9%, ineffective rate 12.5% and recurrent rate 10.7%. The T-lymphocyte subtypes level remarkably increased when compared with that of pre-therapy (46.7+/-3.7 vs 62.5+/-5.5, P<0.01). Our study suggests that chemical destruction of celiac ganglion under ultrasonic guidance is highly safe, and can evidently relieve cancer pain and improve the cellular immunity in patients with advanced pancreatic carcinoma.

Effect of dehydroepiandrosterone on central and peripheral levels of allopregnanolone and β-endorphin

To evaluate the effects of dehydroepiandrosterone (DHEA) oral administration on neuroendocrine function by investigating the modulation exerted by DHEA administration on allopregnanolone and beta-endorphin (beta-EP) central and peripheral levels in ovariectomized rats. Prospective study. Experimental research environment. Female Wistar rats (n = 48). Forty rats were ovariectomized and received an oral treatment with either placebo or 0.5, 1, or 2 mg/kg/day of DHEA. After euthanization, beta-EP levels were measured in hippocampus, hypothalamus, anterior pituitary, neurointermediate pituitary, and plasma. Allopregnanolone and DHEAS levels were measured in hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum. Serum E(2) concentration was also measured. Dehydroepiandrosterone sulfate ester (DHEAS), E(2), beta-EP, and allopregnanolone levels. Dehydroepiandrosterone administration increased DHEAS content in all organs and serum, except for anterior pituitary, where no significant changes occurred. DHEA administration in ovariectomized animals did not significantly increase E(2) circulating levels. DHEA administration induced an increase in allopregnanolone and beta-EP content in hippocampus, hypothalamus, and anterior pituitary and in serum or plasma. Dehydroepiandrosterone administration in ovariectomized animals increased allopregnanolone and beta-EP central and peripheral levels, which suggests that this compound may play a role as a neuroendocrine mediator, possibly substantiating the beneficial effects of postmenopausal DHEA therapy on the central nervous system.

Age-related changes in the oestrous cycle and reproductive hormones in senescence-accelerated mouse

To investigate age-related changes in the oestrous cycle and reproductive hormone levels in senescence-accelerated mouse (SAM), we examined these parameters in 3-, 5-, 7-, 9- and 11-month-old female SAM-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) strains. Levels of beta-endorphin (beta-EP) and substance P (SP) in the hypothalamus were also measured. The oestrous cycle and dioestrus of 9-month-old SAMP8 mice were significantly prolonged compared with age-matched SAMR1 mice. Furthermore, the concentration of serum oestradiol was lower and the level of pituitary luteinising hormone was higher in SAMP8 mice compared with SAMR1 mice. This characterises the hypothalamus-pituitary-ovary (HPO) axis of the SAMP8 strain as hypergonadotropic-hypogonad. The levels of beta-EP and SP in the SAMP8 hypothalamus were lower than in the SAMR1 hypothalamus. These results indicate that the function of the HPO axis in SAMP8 mice declines early and this may be attributed, in part, to the decline in beta-EP and SP concentrations in the hypothalamus.

Exploration on the effect and mechanism of Shenfu injection on resuscitation from general anesthesia

To investigate the effect and the mechanism of Shenfu injection (SFI) on the resuscitation from general anesthesia. Forty patients who received selective abdominal surgery with general anesthesia for 3-4 hrs and ASA grade I-II were divided into two groups, the trial group and the control group, 20 patients in each group. After being sent into the postanesthesia care unit (PACU), the trial group was treated with intravenous dripping of SFI 1.0 ml/kg and the control group was treated with intravenous dripping of equal volume of normal saline. All patients were observed in double blindly manner, the self ventilation recovery time, extubation time, the time of leaving PACU and their Glasgow coma scale (GCS) were recorded and compared. 2 ml of peripheral venous blood were taken to determine the plasma beta-endorphin (beta-EP) content at the time points of before (T1), 5 min (T2), 15 min (T3) and 30 min (T4) after dripping. The self ventilation recovery time, extubation time and time of leaving PACU in the trial group were all shorter than those in the control group (P < 0.01), the GCS in the trial group was better than that in the control group (P < 0.01). The plasma content of beta-EP raised gradually along the recovering of patients consciousness, as compared with the content before dripping (T1), it showed insignificant difference at time point T2 but significant difference at T3 and T4 comparison at the corresponding time point showed that the content at T1 and T2 were similar in the two groups (P > 0.05), but at T3 and T4, the content was higher in the trial group than that in the control group respectively (P < 0.01). SFI could accelerate the resuscitation after general anesthesia, the mechanism may be related with its action in raising plasma beta-EP level.

A microdialysis profile of beta-endorphin and catecholamines in the rat nucleus accumbens following alcohol administration.

Alcohol stimulates the release of dopamine in the nucleus accumbens (NACB) of rats, mice and humans. There is evidence to suggest that the activation of beta-endorphin (beta-EP) in the mesolimbic pathway by alcohol and other drugs of abuse may be associated with the rise in dopamine levels in the NACB. The present studies investigate whether the release of beta-EP in the NACB is (1) dependent on the dose of alcohol that is administered, and (2) associated with changes in the extracellular concentrations of the catecholamines dopamine and norepinephrine, and the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the NACB. Male Sprague-Dawley rats were implanted with a microdialysis probe positioned in the shell region of the NACB. Artificial cerebrospinal fluid was pumped at a rate of 2.3 microl/min in awake and freely moving animals and the dialysate was collected at 30-min intervals. After a baseline period, rats were injected intraperitoneally with either physiological saline or one of three doses of alcohol: 0.8, 1.6, or 2.4 g ethanol/kg body weight. The dialysates collected were analyzed with radioimmunoassay, to estimate the content of beta-EP; and high performance liquid chromatography, to estimate the content of dopamine, norepinephrine, DOPAC and HVA. Alcohol induced a dose-dependent increase in the extracellular levels of beta-EP and dopamine. However, elevations in the extracellular levels of norepinephrine, DOPAC and HVA did not reach significance. The largest increase in beta-EP and dopamine was observed with the 2.4 g/kg dose. The alcohol-induced release of beta-EP and dopamine in the NACB is dose-dependent, where the highest dose resulted in more pronounced concentrations in the dialysate. Furthermore, the increase in the extracellular levels of dopamine appeared to occur at an earlier time point following alcohol administration, than for beta-EP. These results suggest that alcohol stimulates dopamine and beta-EP in the NACB, but probably does so via independent mechanisms.

Plasma levels of beta-endorphin, adrenocorticotropic hormone and cortisol during early and late alcohol withdrawal.

Endogenous opioid peptides are thought to participate in the phenomena of alcohol tolerance and withdrawal. Since in the pituitary gland, beta-endorphin (beta-EP) and adrenocorticotropic hormone (ACTH) are produced from the same precursor molecule, pro-opiomelanocortin, it may be expected that alterations in plasma ACTH and cortisol levels should parallel changes in plasma beta-EP levels during alcohol withdrawal. The aim of the present study was to investigate the alterations of beta-EP, ACTH and cortisol secretion patterns in alcohol-dependent patients with heavy intake in the early withdrawal period and, if any, whether these changes remained stable on long-term withdrawal. Twenty-two hospitalized male patients (mean age +/- SD: 43.45 +/- 9.22 years, mean daily amount of alcohol +/- SD: 421.59 +/- 116.57 g) who were diagnosed to have alcohol withdrawal and 20 age-matched healthy men (mean age +/- SD: 38.35 +/- 7.63 years) were included in the study. Morning and night levels of plasma beta-EP, ACTH and cortisol were measured in the patients during the early (first week) and late (fourth week) withdrawal periods following alcohol cessation, and only once in the control subjects. It was found that both morning beta-EP and morning ACTH levels were reduced during both early and late withdrawals, whereas cortisol levels were increased in early withdrawal and normalized towards the late withdrawal period. The finding that beta-EP deficiency continued despite withdrawal symptoms subsiding in patients suggests that their beta-EP deficiency is independent of the withdrawal syndrome and that reduced beta-EP activity may be a trait contributing to alcohol craving.

Decreased cerebrospinal fluid levels of β-endorphin and ACTH in children with infantile spasms

To investigate the pathophysiology of infantile spasms (IS), we measured the cerebrospinal fluid (CSF) levels of beta-endorphin (beta-EP), adrenocorticotropic hormone (ACTH), and corticotropin-releasing hormone (CRH) in 20 patients with IS, including 11 with the secondary form and 9 with the cryptogenic form of the disease. The findings were compared with those obtained in age-matched controls without neurologic disease. The CSF levels of beta-EP and ACTH were significantly lower in patients with IS than those in the controls. The CSF levels of CRH in patients with IS were lower, although, this trend was not significant. These reductions in the CSF levels of these neuropeptides could explain the impairment of the brain-adrenal axis in such patients. These results might support the hypothesis that, instead of originating from an increased abundance of CRH, which can act as a rapid and potent convulsant, some infantile seizures could be caused by an ACTH deficiency.

Cardiovascular and hormonal responses to hyperthermic stress in cocaine addicts after a long period of abstinence

In order to study the effects of exposure to heat, cardiovascular and hormonal responses were measured in 10 male cocaine addicts (after 4 weeks and 1 year of abstinence) and in 10 normal men. Subjects sat for 30 minutes in a sauna room. Hormonal (ACTH, beta endorphin, (beta EP) met enkephalin (met-enk), prolactin (PRL), cortisol) and cardiovascular parameters (heart rate, systolic and diastolic blood pressure) were measured before and after heat exposure. Basal levels of ACTH, beta EP, Met-Enk and cortisol were similar in normal and in cocaine addicts, whereas plasma PRL values were higher in drug abusers after long-term abstinence. All the examined hormones, with the exception of Met-Enk, were significantly raised in normal control subjects at the end of sauna. In contrast, no significant hormonal response to hyperthermia was observed in cocaine addicts either after 4 weeks and 1 year of abstinence. No changes were detected in heart rate and blood pressure in each group, indicating that the cardiovascular adaptive responses to hyperthermia in cocaine addicts was unaltered. The results of the present study provide evidence of an impairment of the hormonal response to hyperthermia in cocaine abusers. In conclusion, cocaine abuse produces alteration in the hypothalamic-pituitary function which persists after a long period of abstinence.

Effect of TCM on plasma β-endorphin and placental endocrine in threatened abortion

To explore the effect of TCM on plasma beta-endorphin (beta-EP) and placental endocrine function in patients of threatened abortions (TA). Changes of plasma beta-EP, gonadotrophin releasing hormone (GnRH), human chorionic gonadotrophin (HCG), progesterone (P4) levels were measured with RIA in 40 cases of TA with a history of recurrent spontaneous abortion treated with Chinese herbal medicine for reinforcing Kidney and Qi, hemostasis and antiabortion. And the results were compared with those of normal early pregnant women and patients with incomplete abortion as control. The plasma beta-EP level in TA was significantly higher than that in normal pregnant women, P < 0.01. On the contrary, plasma GnRH, HCG and P4 were obviously lower in TA as compared with those of the normal cases, P < 0.01. After treatment, 36 of the 40 patients succeeded in the continuity of pregnancy, their symptoms of TA disappeared, and the above-mentioned four criteria measured at 10-12th week of gestation were similar to those of normal cases, P > 0.05. TCM treatment can regulate plasma beta-EP and placental endocrine function in threatened abortion.

Changes in beta-endorphin and stress-induced analgesia in mice after exposure to forced walking stress

In this study, we attempted to clarify the correlation between changes in the level of beta-endorphin (beta-EP) in the mouse brain and the stress-induced analgesia (SIA) after exposing animals to forced walking stress. The immunohistochemical distribution of beta-EP after stress was first analyzed quantitatively in mice and then more specifically using a microphotometry system with results showing that the fluorescence intensity of beta-EP in the peri-aqueductal gray matter (PAG) and arcuate nucleus of the medial basal hypothalamus (ARC) was increased 6 h after exposure to forced walking stress. Further, SIA was examined after exposing animals to the forced walking stress and the formalin test. At 6 h after forced walking stress, significant SIA was observed in the second phase (from 10 to 30 min after formalin injection) of the formalin-induced paw licking behavior, but not in the first phase (from 0 to 10 min after formalin injection). This SIA was antagonized by beta-EP-(1-27), an opioid epsilon receptor antagonist. In nonstressed mice, the injection of beta-EP produced a reduction in formalin-induced paw-licking in the second phase. A significant antinociceptive effect by beta-EP was well antagonized by beta-EP-(1-27). Thus, the present results suggest that the increase in beta-EP levels in PAG and/or ARC may be involved in SIA after exposure of mice to the forced walking stress.

Effects of Ethanol on α‐Adrenergic and β‐Adrenergic Agonist‐Stimulated β‐Endorphin Release and cAMP Production in Hypothalamic Cells in Primary Cultures

We have previously shown that low concentrations of ethanol rapidly stimulate beta-endorphin (beta-EP) release from hypothalamic neurons in primary cultures and that chronic exposures to these concentrations of ethanol desensitize beta-EP neurons to ethanol challenges. We have also shown that chronic ethanol desensitizes dibutyryl cAMP-, adenosine-, and prostaglandin E1-stimulated beta-EP release and the cAMP content in hypothalamic neurons. In this study, we determined the effects of ethanol (50 mM) on beta-adrenergic agonist (isoproterenol) or alpha-adrenergic agonist (l-phenylephrine)-induced beta-EP release and cellular contents of cAMP to identify whether ethanol causes heterologous desensitization of the adenylate cyclase system in this neuronal cell population. Both isoproterenol and l-phenylephrine increased beta-EP levels in culture media and elevated the cAMP content in cell extracts in a concentration (0.1 and 10 microM)-dependent fashion between 3 to 6 hr. A 50 mM dose of ethanol increased beta-EP and cAMP levels at 3 hr, but it did not elevate beta-EP and cAMP levels after 48 hr of exposure. Acute exposure (3 hr) of these cells to ethanol moderately enhanced the isoproterenol-stimulated and l-phenylephrine-stimulated levels of media beta-EP and intracellular levels of cAMP. However, chronic exposure (48 hr) to ethanol reduced the magnitude of both alpha- and beta-adrenergic receptor agonist-stimulated beta-EP release and cAMP production. These results confirm our previous findings that the ethanol action on beta-EP secretion is mediated by the cAMP system and further suggest that chronic ethanol causes heterologous desensitization of the adenylate cyclase system in the beta-EP neuronal cell population.

Effect of chronic prolactin infusion on pituitary prolactin and hypothalamic proopiomelanocortin.

Although there is evidence that endogenous opioids, and in particular beta-endorphin (beta-EP), may mediate some of the suppressive effects of hyperprolactinemia on the hypothalamic-pituitary-gonadal (HPG) axis, there is controversy about the effects of prolactin (PRL) on beta-EP and its precursor, proopiomelanocortin (POMC), in the hypothalamus. In this study we have therefore examined the effects of chronic peripheral and intracerebroventricular (i.c.v.) infusion of ovine PRL on POMC gene expression and beta-EP levels in the medial basal hypothalamus (MBH) of castrated male and female rats. Endogenous pituitary and plasma PRL levels were determined by RIA with an antiserum to rat PRL which does not crossreact with oPRL. Suppression of endogenous rPRL levels was used as a confirmation of the biological effectiveness of the infused oPRL. POMC mRNA was measured in the MBH by solution hybridization assay. In the first experiment oPRL (5 microg/microl/h) or vehicle was infused for 2 weeks by osmotic minipump into the right lateral ventricle of ovariectomized rats. The mean plasma concentration of rPRL declined from 3.7+/-1.0 ng/ml in the controls to 1.4+/-0.13 ng/ml in the oPRL infused animals (P<0.05); pituitary rPRL content similarly decreased from 39.1+/-4.6 microg to 20.4+/-3.7 microg (P<0.02). There was no significant change in the concentration of POMC mRNA or beta-EP in the MBH of the oPRL treated animals. In the second experiment oPRL was infused for 1 week into the third ventricle of orchiectomized rats. Again despite a fall in endogenous PRL levels, there was no significant change in POMC or beta-EP in the MBH. In the third experiment oPRL was infused subcutaneously into orchiectomized rats for 2 weeks. Mean plasma oPRL levels were 150+/-7.3 ng/ml after 1 week and 58+/-7.5 ng/ml after 2 weeks. Pituitary rPRL content was again suppressed in the oPRL treated animals but no change in POMC or beta-EP was detected in the MBH. We conclude that oPRL can be infused both peripherally and centrally for up to 2 weeks with resulting suppression of endogenous pituitary PRL content and release. Under these conditions no effects on the concentrations of POMC mRNA or beta-EP could be demonstrated in the hypothalamus. These results suggest that either PRL has nongenomic effects on hypothalamic beta-EP or that endogenous opioids other than beta-EP mediate the suppressive effects of PRL on the HPG axis.

ACTH, beta-endorphin, substance P, and corticotrophin releasing hormone in plasma and follicular fluid in hormonally stimulated menstrual cycles for in-vitro fertilization in the human.

Changes in plasma concentrations of ACTH, beta-endorphin (beta-EP) and cortisol have been found to be associated during the human menstrual cycle. Changes in hypothalamic levels of gonadotrophin releasing hormone (GnRH), beta-EP and substance P (SP) have also been associated with the oestrous cycle in the rat. Therefore, an attempt was made to measure the activity of the corticotrophic axis and SP by measuring blood and follicular fluid concentrations of ACTH, beta-EP, SP and corticotrophin releasing hormone (CRH) during the hormonal ovarian stimulation phase for in-vitro fertilization (IVF), in a series of 19 patients. At the plasma level, there was no significant change over treatment days in ACTH (P = 0.1550), beta-EP (P = 0.1137), or SP concentrations (P = 0.5625). CRH was not detectable over treatment days. In addition, there was no significant change in neuropeptide over treatment days between those women who became pregnant and those who did not (P = 0.17 for all). In the follicular fluid, ACTH was not detectable, beta-EP concentration was three times higher than in the plasma, CRH was detectable, and SP concentration was similar to that of plasma. There was no apparent correlation, however, between beta-EP or SP concentrations in the plasma and follicular fluid from a given patient. In conclusion, the absence of changes in the activity of the corticotrophic axis during the hormonal ovarian stimulation suggests that there was no major stress component associated with the stimulation phase of IVF or the occurrence of a pregnancy.

Activation of the hypothalamo-anterior pituitary corticotropin-releasing hormone, adrenocorticotropin hormone and beta-endorphin systems during the estradiol 17 beta-induced plasma LH surge in the ovariectomized monkey.

The present work describes time-dependent changes in the content of corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH), and beta-endorphin (beta-EP) in the hypothalamus (HT) and anterior pituitary (AP) and in the concentration of ACTH and beta-EP in the plasma during the 17 beta estradiol (E2) benzoate (E2B)-induced luteinizing hormone (LH) surge in ovariectomized cynomolgus monkeys. Monkeys were euthanized at 0, 30, 48, 72, and 96 hr post-E2B. HT and AP were rapidly dissected, extracted in 2 N acetic acid containing 1 mM phenylmethane sulfonyl fluoride at 4 degrees C, and centrifuged at 18,000g for 30 min. Peptide concentrations were measured in the supernatant by specific radioimmunoassays (RIAs). In the HT, there were significant (P < 0.05) decreases in ACTH and beta-EP content by 30 hr post-E2B and a significant (P < 0.05) decrease in HT CRH content 48 hr post-E2B. Thereafter, CRH, ACTH, and beta-EP content increased up to 72 hr post-E2B. In the AP, there was an almost linear decrease in the CRH content through 48 hr post-E2B followed by a marked 20-fold (P < 0.01) increase in the AP CRH content at 72 hr post-E2B, which corresponds to the time of the descending arm of the LH surge. The patterns of ACTH and beta-EP content were very similar in the AP, while that of CRH differed markedly. In contrast, in the HT CRH, ACTH, and beta-EP profiles were very similar. Significant (P < 0.05) increases in circulating levels of ACTH, beta-EP, and cortisol were evident at 30 hr (all 3 hormones), 48 hr (beta-EP and cortisol), and 72 hr (cortisol) post-E2B, which corresponds with the time of decreased hypothalamic content of CRH, ACTH, and beta-EP. These results suggest that there maybe a marked activation of the hypothalamo-anterior pituitary-adrenal axis during the negative and positive feedback phases of the E2B-induced LH surge in the ovariectomized monkey.

Diurnal Variation in Luteinizing Hormone-Releasing Hormone and β-Endorphin Release in Pituitary Portal Plasma during the Rat Estrous Cycle1

In this study, we investigated the pattern of both LHRH and beta-endorphin (beta-EP) secretion from the median eminence of cyclic female rats during the estrous cycle by collecting pituitary portal blood for hormone measurements by RIA. On diestrus, proestrus, or estrus (0900 h or 1300 h), rats were hypophysectomized (in order to prevent contamination of portal beta-EP with pituitary beta-EP) and were given a 50-60-min resting period of postsurgical recovery prior to blood sampling. Between 1000 h and 1800 h of the same day, pituitary portal blood samples were collected at 10-min intervals from these animals under Saffan anesthesia. Hormone RIA data revealed that LHRH and beta-EP levels in the portal plasma ranged from 25 to 600 pg/ml and from 0.6 to 4.6 ng/ml, respectively, whereas no discernible amounts of these hormones were detected in the peripheral plasma. Analysis further revealed that secretion of both LHRH and beta-EP showed a diurnal rhythmicity and that both neuropeptides were secreted in a pulsatile manner on each day of the cycle, with most dramatic changes seen in female rats on proestrus. In proestrus rats, portal plasma levels of beta-EP were highest during 1000-1500 h and lower around 1600-1800 h. In contrast, morning and early afternoon values of LHRH were obviously higher in rats on proestrus than in animals on other days of the cycle, and an even greater rise in portal plasma levels of LHRH occurred in late afternoon on proestrus, when beta-EP values were lowest.(ABSTRACT TRUNCATED AT 250 WORDS)