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Biomedical subjects

O Khorram

Publications and source records attributed to O Khorram.

At least 37 records · Page 2Linked to original sources
PubMed1989

Simultaneous induction of neuropeptide Y and gonadotropin-releasing hormone release in the rabbit hypothalamus.

Neuropeptide Y (NPY) can induce the release of endogenous mediobasal hypothalamic gonadotropin-releasing hormone (MBH-GnRH) and pituitary gonadotropins, especially LH. In these studies, we monitored changes in endogenous NPY concentrations at 20-min intervals for 6-8 h during push-pull perfusion (PPP) in both the mediobasal hypothalamus (MBH) and the third cerebroventricle (3VT) of ovarian intact, conscious rabbits. Because previous studies had shown that copper ion can induce hypothalamic GnRH release, cupric acetate (CuAc) was administered either intravenously or intraventricularly during the PPP to manipulate changes in NPY concentrations. Our results show that NPY concentrations in both MBH and 3VT PPP samples were detectable by radioimmunoassay. Administration of CuAc sharply increased hypothalamic NPY release within the same time interval as that for induction of hypothalamic GnRH release. The results are consistent with the hypotheses that NPY may act as a neuromodulator for hypothalamic GnRH secretion, or that common mechanisms drive secretion of these two neuropeptides.

Animals↗
PubMed1987

Alpha-melanocyte stimulating hormone discloses a stimulatory effect of beta-endorphin on somatostatin release.

The influence of alpha-melanocyte stimulating hormone (alpha-MSH) and beta-endorphin (beta-END) on the secretion of somatostatin (SRIF) from the median eminence (ME) was studied using an in vitro incubation system. The MEs from adult male rats were first preincubated at 37 degrees C for 30 min with constant shaking in 0.4 ml of Krebs-Ringer bicarbonate-glucose buffer (pH 7.4) containing bacitracin in an atmosphere of 95% O2/5% CO2. Medium was discarded and replaced by medium containing different doses of alpha-MSH, beta-END, or a fixed dose of alpha-MSH (10(-7) M or 10(-9) M) plus beta-END at various concentrations. By themselves alpha-MSH and beta-END did not alter basal SRIF release, but in the presence of alpha-MSH (10(-7) M) beta-END stimulated somatostatin release. This effect was significant at concentrations of beta-END of 10(-8) M and higher. The permissive effect of alpha-MSH was observed at a concentration as low as 10(-9) M, but in this case the stimulatory effect of beta-END became evident only at higher doses tested (10(-7) M). It is suggested that alpha-MSH and beta-END participate in the modulation of SRIF release. By themselves beta-END and alpha-MSH did not affect basal release of SRIF but in the presence of alpha-MSH, beta-END had a stimulatory effect on SRIF release. The mechanism for this interaction is unknown. The results are consistent with the possibility that beta-END neurons have stimulatory and inhibitory effects on SRIF release and that alpha-MSH, by blocking the inhibitory components, discloses the stimulatory effect of beta-END on SRIF release.

Adrenocorticotropic Hormone↗
PubMed1987

Role of opioid peptides in pulsatile release of gonadotropins and prolactin in the rat.

To determine the role of endogenous opioid peptides in the pulsatile release of gonadotropins and prolactin in the ovariectomized rat, the opiate receptor blocker, naloxone, was administered intravenously, and its effect on plasma FSH, LH and prolactin was determined by multiple sampling prior to and after injection. Naloxone produced a dose-related increase in plasma LH and to a lesser extent FSH and decreased prolactin levels in the experiment in which they were examined. Higher doses of naloxone produced a significant increase in plasma LH pulse amplitude and lengthened the interpulse interval with a consequent decrease in pulse frequency. Minimum values between pulses were also increased. There was no clear effect on FSH pulsations but pulses of prolactin were blocked. Intraventricular (third ventricle) injection of a specific anti beta endorphin antiserum (3 microliter) produced an initial decline followed by an elevation of LH but had no effect on plasma FSH. The normal rabbit serum control injections were without effect. It is hypothesized that initiation of LH pulses in the castrated rat may be related to a periodic removal of tonic beta endorphinergic tone.

Animals↗
PubMed1987

The role of brain peptides in neuroimmunomodulation.

Since neuroimmunomodulation is brought about in part, at least, by secretion of pituitary hormones involved in stress and immune responses, we review briefly the hypothalamic control of the release of ACTH, growth hormone, and prolactin. The release of ACTH is controlled particularly by corticotropin-releasing factor (CRF), but vasopressin has intrinsic releasing activity and potentiates the action of CRF at both hypothalamic and pituitary levels. Oxytocin may even potentiate the action of CRF, but has little, if any, ACTH-releasing activity by itself. In addition, epinephrine may augment responses to the CRFs. In contrast, growth hormone is under dual control by growth-hormone-releasing factor (GRF) and somatostatin, and prolactin is under multifactorial control by a series of inhibitors and stimulators. Dopamine is accepted as a physiological prolactin-inhibiting factor (PIF), but probably GABA and possibly acetylcholine as well are PIFs. There is good evidence for a peptide PIF as well. There are a number of prolactin-releasing factors (PRFs) which include oxytocin, vasoactive intestinal polypeptide, PHI and TRH. Several other peptides can also release prolactin, including angiotensin II. In response to stress there is a complex interaction of peptides intrahypothalamically. CRF augments its own release by an ultra short-loop positive feedback, and there is negative ultra short-loop feedback of GRF and somatostatin. Vasopressin appears to augment CRF release as well as to act directly on the pituitary, and there are complex interactions of various peptides to influence prolactin and GH release.

Adjuvants, Immunologic↗
PubMed1987

Bimodal effects of neuropeptide Y on hypothalamic release of gonadotropin-releasing hormone in conscious rabbits.

Neuropeptide Y (NPY) is present in large quantities in the hypophysiotropic areas of the brain and has a similar distribution pattern as gonadotropin-releasing hormone (GnRH). The aim of this study was to measure GnRH release during perfusion of NPY through the mediobasal hypothalamus of intact and ovariectomized (OVEX) does. Does were fitted with push-pull (PP) cannulae directed into the median eminence and were subjected to subsequent PP perfusion at a flow rate of 20 microliters/min for a total of 6 or 8 h. Six intact does and seven OVEX does received intrahypothalamic perfusion of NPY (14 micrograms/ml) for either 2 or 3.5 h during the 6 or 8 h, respectively, of PP perfusion. The PP samples and femoral vein blood samples were collected at 10-min intervals on ice. Perfusate GnRH and plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) levels were measured by specific radioimmunoassays. The pulsatile parameters of all hormones were analyzed by the 'PULSAR' program. Perfusion of NPY significantly decreased mean levels, pulse amplitudes, and pulse frequencies of GnRH in OVEX does. Also, mean levels of LH were decreased, whereas levels of FSH and PRL were unaffected by NPY. In contrast to these inhibitory effects on GnRH in OVEX does, the same NPY perfusion stimulated mean levels and pulse amplitudes of GnRH in intact does. Plasma levels of neither gonadotropin nor PRL were affected significantly by the NPY treatment in intact rabbits. These results indicate that NPY may have central effects on neuronal release of GnRH, and that ovarian factors are critical in the directional mode of these NPY actions.

Animals↗
PubMed1986

The influence of suckling on the hypothalamic and pituitary secretion of immunoreactive alpha-melanocyte stimulating hormone.

The effect of suckling on the secretion of alpha-melanocyte stimulating hormone (alpha-MSH) from the hypothalamus and pituitary was determined by a specific radioimmunoassay. There was an increase in the neurointermediate lobe (NIL) content of alpha-MSH 1 h after the onset of suckling. The values were restored to control levels within 3 h. The anterior lobe content of alpha-MSH was not affected by suckling. Plasma alpha-MSH levels were also unaffected by suckling, indicating that suckling probably affects the synthesis of NIL alpha-MSH, and not its release. Suckling lowered the alpha-MSH content in the mediobasal hypothalamus of lactating rats, and had no effect on the median eminence content of this peptide. In vitro, hypothalami from lactating rats released more alpha-MSH than hypothalami of random cycling females under basal, and stimulated (56 mM potassium) conditions. These results suggest that hypothalamic alpha-MSH may play a role in mediating some of the hormonal changes occurring during lactation.

Animals↗
PubMed1986

Central administration of alpha-MSH antiserum augments fever in the rabbit.

alpha-Melanocyte-stimulating hormone (alpha-MSH) has a marked antipyretic action when given centrally or peripherally, and the concentration of this peptide within the septal region of the brain increases during fever. To assess the significance of endogenous central alpha-MSH in fever, antiserum was given to rabbits via a cannula implanted in the third cerebral ventricle. Each day for 3 days, the animals received 50 microliters of normal rabbit serum (NRS) or an equal volume of antiserum raised against alpha-MSH. Interleukin 1 (IL 1) was then injected intravenously to determine the effect of central immunoneutralization of alpha-MSH on the febrile response. Immunoneutralization markedly prolonged fever. The average rise in temperature and the area under the fever curve after IL 1 injection were also significantly increased. Antiserum treatment did not alter normal body temperature, and NRS had no effect on IL 1-induced fever. These results indicate that endogenous central alpha-MSH contributes to physiological limitation of fever and that the role of this peptide in temperature regulation is relevant to the febrile state but not to normothermia.

Animals↗
PubMed1986

On the presence of a nondopaminergic, peptidergic prolactin release-inhibiting factor in hypothalamic extracts of infantile rats.

Crude hypothalamic extracts prepared from brains of 1-day-old rats produced a dose-dependent inhibition of prolactin (Prl) release by adult male hemipituitaries, and to a lesser extent by hemipituitaries of adult ovariectomized (OVX), estrogen-primed rats. These extracts contained 6-fold lower levels of dopamine than adult hypothalami. The inhibitory effect of the adult hypothalamic extracts, contrary to infantile hypothalamic extracts could be blocked by spiroperidol. Digestion of the infantile hypothalamic extracts with pronase totally abolished their Prl release-inhibiting activity, indicating the peptidic nature of this inhibitory substance. In contrast to their effect on Prl release by hemipituitaries, infantile hypothalamic extracts stimulated Prl release from dispersed anterior pituitary cells of OVX estrogen-primed rats, pointing to the importance of estrogen in modulating prolactin release-inhibiting factor (PIF) activity and the possibility that the PIF receptor is trypsin-sensitive.

Age Factors↗
PubMed1986

Interaction of alpha-melanocyte-stimulating hormone with beta-endorphin to influence anterior pituitary hormone secretion in the female rat.

The interaction of alpha MSH and beta-endorphin on the secretion of PRL, GH, and LH was determined in the ovariectomized rat. The potent stimulatory effect on PRL release of injection of 20 ng (5.8 pmol) beta-endorphin into the third cerebral ventricle was completely blocked by 100 ng (60 pmol) alpha MSH. The same dose of alpha MSH partially blocked the effect of 150 ng (44 pmol) beta-endorphin on PRL secretion. Intraventricular injection of either 20 ng beta-endorphin or 100 ng alpha MSH had no effect by itself on plasma LH. However, coinjection of these doses of beta-endorphin and alpha MSH suppressed plasma LH levels significantly within 15 min. beta-Endorphin (150 ng) produced a significant suppression of plasma LH levels. Furthermore, coadministration of 100 ng alpha MSH with 150 ng beta-endorphin lowered plasma LH for a longer period of time than this dose of beta-endorphin alone. Low doses of beta-endorphin (20 ng) or alpha MSH (100 ng) alone or in combination did not alter plasma GH levels. A higher dose of 150 ng beta-endorphin produced a slight elevation of plasma GH. This effect was potentiated 5-fold when 150 ng beta-endorphin were injected in combination with 100 ng alpha MSH. These results indicate that alpha MSH acts as an antagonist to beta-endorphin in regard to the secretion of PRL, whereas it potentiates the effect of beta-endorphin in stimulation of GH and inhibition of LH secretion.

Animals↗
PubMed1985

Role of arginine vasopressin in control of ACTH and LH release during stress.

To determine the role of arginine vasopressin (AVP) in stress-induced release of anterior pituitary hormones, AVP antiserum or normal rabbit serum (NRS) was micro-injected into the 3rd ventricle of freely-moving, ovariectomized (OVX) female rats. A single 3 microliter injection was given, and 24 hours later, the injection was repeated 30 min prior to application of ether stress for 1 min. Although AVP antiserum had no effect on basal plasma ACTH concentrations, the elevation of plasma ACTH induced by ether stress was lowered significantly. Plasma LH tended to increase following ether stress but not significantly so; however, plasma LH following stress was significantly lower in the AVP antiserum-treated group than in the group pre-treated with NRS. Ether stress lowered plasma growth hormone (GH) levels and this lowering was slightly but significantly antagonized by AVP antiserum. Ether stress also elevated plasma prolactin (Prl) levels but these changes were not significantly modified by the antiserum. To evaluate any direct action of AVP on pituitary hormone secretion, the peptide was incubated with dispersed anterior pituitary cells for 2 hours. A dose-related release of ACTH occurred in doses ranging from 10 ng (10 p mole)-10 micrograms/tube, but there was no effect of AVP on release of LH. The release of other anterior pituitary hormones was also not affected except for a significant stimulation of TSH release at a high dose of AVP. The results indicate that AVP is involved in induction of ACTH and LH release during stress. The inhibitory action of the AVP antiserum on ACTH release may be mediated intrahypothalamically by blocking the stimulatory action of AVP on corticotropin-releasing factor (CRF) neurons and/or also in part by direct blockade of the stimulatory action of vasopressin on the pituitary. The effects of vasopressin on LH release are presumably brought about by blockade of a stimulatory action of AVP on the LHRH neuronal terminals.

Adrenocorticotropic Hormone↗
PubMed1985

Fever-specific changes in central MSH and CRF concentrations.

The concentration of melanocyte-stimulating hormone (melanotropin; MSH) within the septal region of the brain increases during the fever, and septal injections of MSH are antipyretic. Corticotropin-releasing factor (CRF), when injected intracerebroventricularly, is also antipyretic. Using sensitive radioimmunoassays of microdissected tissue extracts, we established the presence of immunoreactive MSH (IRMSH) and CRF (IRCRF) within discrete central nervous system sites of the rabbit. Leukocytic pyrogen-induced fever and hyperthermia due to heat exposure did not alter concentrations of IRMSH or IRCRF in tissue extracted from preoptic-anterior hypothalamic or midbrain central gray regions. However, significantly greater levels of IRMSH were detected in septal extracts of febrile rabbits than in similar extracts from afebrile controls or heat-stressed animals. A significant decrease in IRCRF was detected in paraventricular nucleus extracts from febrile animals compared with extracts from afebrile controls or heat-stressed rabbits. Our results support the hypothesis that these central peptides have a role in temperature control during fever. Since no changes were detected in extracts from hyperthermic rabbits, it appears that changes in concentration of these neuropeptides within particular brain regions are specific to the febrile state and are not caused by elevation of body temperature or by nonspecific stress.

Animals↗
PubMed1985

Age-, sex-, and gonadal steroid-related changes in immunoreactive substance P in the rat anterior pituitary gland.

The interrelationship of anterior pituitary lobe (AP) immunoreactive substance P (I-SP) concentrations with age, sex, gonadal steroids, and estrous cyclicity in rats was examined. There was no difference between male and female AP I-SP levels at 0.5 month of age. At 2.0 and 5.0 months of age, a sex-linked difference in AP I-SP concentrations was evident, inasmuch as male APs contained approximately 3 and 8 times greater concentrations of I-SP, respectively, than APs from age-matched females. Long term (6 weeks) gonadectomy of adult rats resulted in an increase in I-SP concentrations in female APs and a decrease in the concentrations of the peptide in male APs compared to values in their respective sham-operated controls. Treatment of gonadectomized animals for the same length of time with gonadal steroid-filled Silastic capsule implants resulted in qualitatively identical responses in males and females; that is, estradiol benzoate decreased and 5 alpha-dihydrotestosterone propionate increased AP I-SP levels compared to the respective control values in castrates. Testosterone propionate treatment had no effect on AP I-SP levels compared with the respective gonadectomy control values. Short term (8 days) gonadectomy of adult males did not affect the AP concentration of I-SP. Likewise, gonadectomy of adult females was ineffective in altering the AP I-SP concentration compared with concentrations in females on diestrous day 1, diestrous day 2, proestrous, or estrous stages of the vaginal cycle. These data suggest that gonadal steroids are physiologically important in the regulation of I-SP concentrations in the AP. We hypothesize that I-SP is indigenous to the AP and that gonadal steroids act directly at the level of the AP to affect the synthesis and/or release of the peptide.

Age Factors↗
PubMed1985

Stress-induced secretion of alpha-melanocyte-stimulating hormone and its physiological role in modulating the secretion of prolactin and luteinizing hormone in the female rat.

The pattern of alpha MSH release during immobilization stress in ovariectomized rats was determined and correlated with that of plasma PRL and LH. Stress induced a marked elevation in plasma immunoreactive alpha MSH, with a time course identical to that of plasma PRL. The increment in plasma PRL was greater than that in plasma alpha MSH. Plasma LH was markedly lowered by stress. Analysis of pituitary and hypothalamic alpha MSH indicated a significant (P less than 0.05) increase in the neurointermediate lobe and anterior lobe content of alpha MSH. The alpha MSH content in the hypothalamus was lowered by stress when expressed as tissue content (P less than 0.025), although no significant differences in content in this area were detected when the results were expressed in terms of tissue protein. Stress induced a marked increase (P less than 0.01) in the median eminence levels of alpha MSH. Intraventricular (third ventricle) injection of the gamma-globulin fraction of a specific antiserum raised against alpha MSH increased basal PRL levels (P less than 0.025) and prevented the decline in plasma PRL that occurred 60 min after the onset of stress in the normal rabbit serum-injected rats. The stress-induced suppression of plasma LH was attenuated and delayed by the administration of alpha MSH antibodies. In conclusion, alpha MSH of brain origin is released during stress and is involved in lowering plasma PRL to basal levels and producing a partial suppression of plasma LH.

Animals↗
PubMed1985

Purification of a non-dopaminergic and non-GABAergic prolactin release-inhibiting factor (PIF) in sheep stalk-median eminence.

Prolactin release-inhibiting factor (PIF) extracted from 1200 sheep stalk-median eminences was purified by gel filtration on a Sephadex G-25 column (4.5 X 150 cm). PIF activity was determined by measuring the inhibition of prolactin release from dispersed anterior pituitary cells of adult male or estrogen-primed, ovariectomized rats. Using this system, PIF was detected in tube fractions 122-127 (volume = 20 ml/tube). These fractions also contained LHRH and somatostatin; however, these peptides had no prolactin-inhibiting activity in the quantities present. No dopamine or gamma-aminobutyric acid (GABA) was detected in the active fractions by radioenzymatic assay and fluorophotoenzymatic assay, respectively. Furthermore, receptor blockers for dopamine or GABA did not interfere with the PIF activity. These findings indicate that the PIF activity cannot be attributed to either dopamine or GABA, both of which are known to inhibit prolactin release, and provide evidence for the presence of a non-dopaminergic and non-GABAergic PIF within the hypothalamus.

Animals↗
PubMed1985

Possible negative ultra-short loop feedback of luteinizing hormone releasing hormone (LHRH) in the ovariectomized rat.

To determine if LHRH might act within the brain to modify its own release, repeated blood samples were removed from conscious ovariectomized rats and minute doses of LHRH were injected into the third ventricle (3V). The effect of these injections on plasma LH and FSH was measured by radioimmunoassay (RIA). The higher dose of intraventricular LHRH (10 ng in 2 microliter) induced an increase in plasma LH within 10 min after its injection. Plasma LH decreased for the next 60 min. This was followed by restoration of LH pulses characteristic of the ovariectomized rat. This dose of LHRH slightly elevated plasma FSH concentrations. In stark contrast, a 10 fold lower dose of 1 ng of LHRH injected into the ventricle resulted in a highly significant decrease of plasma LH at 10 min following injection, followed by return of LH pulsations. There was no effect on the pulsatile release of FSH. The results are interpreted to mean that at the higher dose, sufficient LHRH reached the site of origin of the hypophyseal portal vessels in the median eminence so that it diffused into portal vessels and was delivered to the gonadotrophs to induce LH release. In contrast, the lower dose provided sufficient hypothalamic concentrations of the peptide to suppress the discharge of the LHRH neurons, thereby leading to a decline in plasma LH, indicative of an ultrashort-loop negative feedback of LHRH to suppress its own release.

Animals↗
PubMed1984

Partial characterization of immunoreactive substance P in the rat pituitary gland.

Two distinct carboxy-terminus-directed anti-substance P (SP) sera (R-1C and R-6G) were used to characterize immunoreactive SP (I-SP) in acetic acid extracts of anterior pituitary (AP) and posterior pituitary (PP) glands of adult male rats. The tissue concentrations of I-SP measured by R-1C and R-6G were comparable. The contents of I-SP were 600-1150 pg/AP and 25-52 pg/PP. I-luteinizing hormone releasing hormone and I-somatostatin (I-SOM) were undetectable in AP extracts, but PP extracts contained the equivalents of 325-785 pg I-SOM/gland. Serial dilutions of AP and PP extracts produced displacement curves with both SP antisera that were parallel to the respective synthetic SP standard and hypothalamic extract displacement curves. Gel filtrations of AP and PP extracts on a Sephadex G-25 column produced I-SP peaks eluting in the same fractions as synthetic SP and hypothalamic I-SP. However, the AP I-SP profile also revealed a side peak migrating between the void volume and the major I-SP peak. Neither immunoreactive species in the AP extract were eliminated when eluted with 6.0 M guanidine HCl, a strong denaturing agent. In vitro incubation of paired anterior hemipituitaries for 30 min in the presence of a 56 mM K+ concentration resulted in a significant (p less than .0001), 25-fold increase in the release of I-SP into the incubation medium above the mean control value. Radiofrequency lesions placed in the median eminence-arcuate region of male rats caused a significant (p less than .001) reduction of I-SP in both the AP and PP. These reductions were inversely related to the plasma prolactin values. The elevation in plasma prolactin was taken as an index of completeness of lesions. We conclude that: 1) the rat pituitary contains I-SP as assessed by its immunologic and chromatographic behavior, 2) K+ depolarization is a potent stimulator of the release of AP I-SP in vitro, 3) the ME-arcuate region is important for the maintenance of pituitary I-SP levels in the rat.

Amino Acid Sequence↗
PubMed1984

Recent studies on the role of brain peptides in control of anterior pituitary hormone secretion.

Recent work in our laboratory on the role of peptides to influence release of pituitary hormones by direct action on the gland and also some of the interactions of these peptides at the hypothalamic level to alter release of pituitary hormones will be reviewed. Considerable evidence from hypothalamic stimulation and lesion studies suggests the existence of a separate FSH-releasing factor (FSHRF). We have been able to purify a bioactive FSHRF which appears to be distinct from LHRH. Consequently, we believe that a distinct FSHRF will ultimately be isolated. With regard to prolactin, it is now clear that it is under dual control by both prolactin-inhibiting (PI) and prolactin-releasing factors (PRF). Although dopamine acts as a PIF, our recent fractionation studies indicate the existence of a peptidic PIF in hypothalamic extracts which can be separated from dopamine and GABA. The peptidic PIF is eluted from Sephadex in the same position originally described by us a number of years ago. Thus, inhibitory control is probably mediated by a combination of factors which would include dopamine, possibly GABA and a peptidic PIF. A number of peptides have been shown to have PRF activity which include TRF and also VIP. In recent studies, we have shown a prolactin-releasing action of oxytocin on male hemipituitaries or dispersed pituitary cells. Furthermore, high doses of oxytocin given intravenously released prolactin in male rats. There is a correlation between estrogen-induced prolactin release and an increase in plasma oxytocin and a correlation between suckling-induced oxytocin and prolactin release. These results suggest that oxytocin may be an important PRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗