Biomedical subjects

O Khorram

Publications and source records attributed to O Khorram.

47 records · Page 3Linked to original sources

PubMed1984

Physiological role of alpha-melanocyte-stimulating hormone in modulating the secretion of prolactin and luteinizing hormone in the female rat.

Long-term ovariectomized (OVX) rats were injected in the third cerebral ventricle with 5 microliter of the globulin fraction of an antiserum raised against alpha-melanocyte-stimulating hormone (alpha-MSH) or an equal volume of the globulin fraction of normal rabbit serum (NRS). Immunoneutralization of brain alpha-MSH produced an increase in the area under the secretion curve of prolactin (Prl), the amplitude of Prl pulses, and mean plasma Prl (P less than 0.01). In animals that had received two injections of NRS or anti-MSH and were subjected to a 2-min ether stress, Prl levels significantly increased within 5 minutes in the NRS-injected rats, whereas Prl levels in the antiserum-injected rats did not increase any further from the initially high baseline levels. The administration of antibodies against alpha-MSH produced a small increase (P less than 0.05) in the area under the secretion of luteinizing hormone (LH) and mean plasma LH; however, the number of LH pulses was unaffected. We conclude that endogenous alpha-MSH of central origin is a physiological neuromodulator of release of Prl and LH in the OVX rat and is involved in the stress-induced release of Prl.

Animals↗

PubMed1984

Pre- and postnatal developmental changes in hypothalamic and pituitary content of alpha-melanocyte-stimulating hormone and somatostatin in the rat.

The developmental pattern of hypothalamic and pituitary somatostatin and alpha-melanocyte-stimulating hormone (alpha-MSH) was studied in the rat by radioimmunoassay (RIA). Prenatally hypothalamic somatostatin was low and the first increase in content occurred on day 5 of the postnatal period. Pituitary somatostatin was undetectable prenatally and was first detected on day 6 postnatally. Pituitary somatostatin showed the same development pattern as hypothalamic somatostatin. Whole pituitaries were analyzed from the fetuses and neonates. Analysis of anterior and posterior lobes from adults revealed that all the somatostatin was in the posterior lobe. Therefore, it is believed that the somatostatin found in the glands of the younger animals was in the neural lobe. alpha-MSH was detected in the fetal hypothalamus as early as day 16, with a marked increase occurring on day 19 prenatally and a further increase on day 10 postnatally. Pituitary alpha-MSH content, readily detectable on the first day examined, i.e. day 16 of the fetal period, increased throughout development. The effect of alpha-MSH on the release of growth hormone in vitro from pituitaries of rats of various ages was tested. alpha-MSH had no effect on growth hormone release.

Animals↗

PubMed1984

The effect and possible mode of action of alpha-melanocyte-stimulating hormone on gonadotropin release in the ovariectomized rat: an in vivo and in vitro analysis.

This study was designed to examine the possible effects of alpha MSH on gonadotropin release. Injection of alpha MSH into the third ventricle of the brain and sampling at 5, 10, 15, 30, and 60 min postinjection produced a significant lowering of plasma LH, but not of FSH, in conscious ovariectomized (OVX) rats. The minimum effective dose was 1 microgram. This procedure did not affect plasma levels of LH or FSH in estradiol benzoate-primed, OVX rats. Multiple blood sampling every 10 min before and after intraventricular injection of alpha MSH (2 micrograms) produced a significant reduction in the area under the secretion curve of LH. Intravenous injection of alpha MSH had little effect; however, a slight lowering of plasma LH occurred in OVX rats after a 50-micrograms dose. The effect of alpha MSH on LH release was blocked by pretreatment of the animals with alpha-methyl-paratyrosine, an inhibitor of catecholamine synthesis, as well as by pretreatment with an iv injection of spiroperidol, a dopamine receptor blocker. The peptide failed to alter basal or K+-stimulated LHRH release from median eminence fragments of OVX rats incubated in vitro. Alpha MSH had no effect on LHRH-induced LH release in vivo and failed to alter the release of FSH and LH from hemipituitaries of OVX rats or dispersed cells from OVX, estradiol benzoate-primed rats in vitro. It is concluded that alpha MSH exerts an inhibitory effect on LH release by an action on the hypothalamus, probably via activation of the tuberoinfundibular dopaminergic system.

Animals↗

PubMed1984

Hypothalamic control of prolactin secretion during the perinatal period in the rat.

The development of hypothalamic control of PRL secretion in the late prenatal and early postnatal periods in the rat was studied by employing a static system for incubation of pituitaries. PRL was detected in the incubation medium after incubating fetal pituitaries as early as day 18. A gradual increase in the amount of hormone released into the medium occurred during development, with the greatest change occurring between days 20 and 21 prenatally. A progressive increase in the pituitary content of PRL occurred during development. The percentage of PRL released from the gland was higher pre- (19-39%) than postnatally (17%). Hypothalamic extracts from fetuses and neonates stimulated the secretion of PRL when coincubated with pituitaries from animals of the same age. However, extracts from 1-day-old neonates inhibited PRL secretion from adult male hemipituitaries. Extracts prepared from adult male hypothalami stimulated PRL secretion from neonatal pituitaries from rats at 1 day of age, as did cerebral cortical extracts from adults, but not 1-day-old, rats. TRH significantly stimulated PRL secretion in vitro from pituitaries of donors as early as day 19 of the fetal period. The response of the pituitaries to this peptide diminished by day 8 postnatally. Immunoneutralization of hypothalamic TRH significantly decreased but did not abolish the PRL-releasing activity of hypothalamic extracts, whereas this procedure had no effect on the GH-releasing activity of the extracts. The dopamine receptor agonist apomorphine (10(-5) M) inhibited PRL secretion in vitro on day 19 of the fetal period and postnatally starting on day 1. The response to apomorphine increased with advancing age. The results suggest that a combination of factors contribute to maintaining high circulating PRL levels during the late fetal and early neonatal periods. These include high rates of PRL release by the pituitary and a relative insensitivity of the pituitary to dopamine in the face of high sensitivity to PRL-releasing factors such as TRH.

Aging↗

PubMed1984

Changes in hypothalamic and pituitary content of immunoreactive alpha-melanocyte-stimulating hormone during the gestational and postpartum periods in the rat.

alpha-Melanocyte-stimulating hormone (alpha-MSH) was measured in the mediobasal hypothalamus (MH), median eminence (ME), preoptic-suprachiasmatic area (POA-SCN), anterior (AL), and posterior lobes (PL) of the pituitary gland during the gestational and postpartum periods in the rat. The content of alpha-MSH in the MH and POA-SCN compared to estrous levels was lower during the later days of gestation and decreased further in the MH during lactation in association with the elevated plasma prolactin (Prl). Distinct increases in the ME content of alpha-MSH compared to estrous levels occurred on Days 8 and 12 of the gestational period and Day 14 of the postpartum period. A significant increase in PL content of alpha-MSH compared to Days 5-11 and 17-20 occurred on Day 4 of gestation, and no significant changes were detected in the AP concentration of alpha-MSH throughout the period studied. In vitro, PLs and ALs from females on Day 4 of gestation secreted more alpha-MSH into the incubation medium than tissues from animals on Day 20. These results suggest that alpha-MSH of both brain and pituitary origin may play a role in mediating some of the physiological changes which occur during pregnancy and lactation.

Animals↗

PubMed1983

Blockade of stress-induced prolactin release in monosodium glutamate-treated rats.

To elucidate the role of the medial basal hypothalamus (MBH) in stress-induced prolactin (Prl) release, adult male rats which had received monosodium glutamate (MSG 4 mg/g) on alternate days for the first 10 days of life were subjected to ether stress for 2 min. Blood samples were drawn at 0, 15, 30 and 60 min after etherization through an indwelling jugular catheter implanted 1 day before the experiment. Sixty minutes after etherization the dopamine receptor blocker spiroperidol (0.1 mg/kg) was injected intravenously and another blood sample was withdrawn 60 min later. Although there were no differences in basal levels of plasma Prl between control and MSG-treated animals, a dramatic elevation of plasma Prl was observed in control rats 15 min after etherization, whereas no significant change was seen in MSG-treated animals. Spiroperidol significantly increased plasma Prl in both groups of animals, but the magnitude of the increase in Prl levels of MSG-treated rats was roughly one-third (p less than 0.005) that of control animals. When morphine (3 mg/kg) was injected to test its capability to stimulate Prl release in MSG-treated rats, significant increases of similar magnitude of plasma Prl were observed in both groups. These results show that (1) the tuberoinfundibular dopaminergic system is functioning in MSG-treated rats to maintain Prl at low levels, (2) the stimulatory effect of morphine on Prl release is intact in MSG-treated rats, and (3) the tuberoinfundibular dopaminergic system is not responsible for stress-induced Prl release, but rather another mechanism located within the arcuate nucleus (ARC) and highly sensitive to destruction by MSG mediates stress-induced Prl release.

Animals↗

PubMed1983

Development of hypothalamic control of growth hormone secretion in the rat.

The development of hypothalamic control of GH in the late prenatal and early postnatal periods in the rat was studied by employing a static system for the incubation of pituitaries. The basal secretion of GH into the medium after a 3-h incubation period showed a gradual increase from day 18 prenatally to day 1 postnatally. This was followed by a gradual decline in GH release on postnatal days 5 and 8. There was a sustained rise in the total pituitary GH content from prenatal day 18 to postnatal day 8. The percentage of the total GH that was released into the medium was high from fetal pituitaries and lower from neonatal pituitaries. TRH (100 ng/ml) stimulated GH secretion starting on prenatal day 21. This TRH effect persisted through day 8 postnatally. Hypothalamic extracts from fetuses and neonates stimulated the secretion of GH when coincubated with pituitaries of the same age and with adult male rat pituitaries. Similarly, adult male rat hypothalamic extract stimulated the secretion of GH from pituitaries of 1-day-old neonates. Pronase treatment of neonatal hypothalamic extract completely abolished its stimulatory effect on GH release. Incubation of 1-day postnatal pituitaries with cerebral cortical extract obtained from neonates of the same age did not alter the secretion of GH; however, cerebral cortical extract from adult males did cause a significant stimulation of GH release from the neonatal pituitaries. Somatostatin (100 ng/ml) failed to inhibit GH release by pituitaries until day 5 postnatally, but a 10-fold increase in the concentration of somatostatin significantly inhibited GH secretion from pituitaries of rats as early as day 21 prenatally. Coincubation of hypothalamic extract with the high concentration of somatostatin significantly attenuated the effect of the extract in stimulating GH release from pituitaries of 1-day-old rats. The results suggest that the high circulating levels of GH during the late prenatal and early neonatal periods are maintained by a combination of factors including the release of a hypothalamic peptidergic GH-releasing factor, the relative insensitivity of the pituitary to somatostatin, and changes in the relative size of storage vs. releasable pools of GH during development.

Aging↗

PubMed1982

Effect of alpha-melanocyte-stimulating hormone on basal and stimulated release of prolactin: evidence for dopaminergic mediation.

The effects of alpha-melanocyte-stimulating hormone (alpha-MSH) on basal and stimulated of prolactin were studied. Intraventricular (i.v.t.) injection of 2 microgram of alpha-MSH in ovariectomized (OVX) rats produced a 50% depression of plasma prolactin levels within 10 min, whereas 100 ng of alpha-MSH or saline had no effect. 2 microgram of alpha-MSH (i.v.t.) produced a more dramatic and sustained depression of prolactin levels if initial prolactin concentrations were elevated. This dose of alpha-MSH was also effective in lowering plasma prolactin levels in OVX rats, primed 72 h earlier with 50 microgram of estradiol benzoate (s.c.), although this depression was of lower relative magnitude than in the unprimed OVX animals. The intravenous injection of a dopamine receptor blocker, spiroperidol (0.1 mg/kg), prior to (i.v.t.) alpha-MSH blocked the inhibitory effect of alpha-MSH on prolactin release. In vitro, alpha-MSH in doses ranging from 0.5 to 5 microgram did not alter prolactin release from hemipituitaries of male or OVX female rates and from dispersed pituitary cells from female rats. These results suggest that alpha-MSH can modulate prolactin release possibly via the hypothalamic dopaminergic system, and that this modulation may be of greater significance during stress.

Animals↗

PubMedDate not supplied

The effect of the estrous cycle and estrogen on the release of immunoreactive alpha-melanocyte-stimulating hormone.

Circulating levels and tissue content of alpha-MSH were measured on the morning of various days of the estrous cycle, and on the afternoon of proestrus in freely moving conscious rats. No surges of alpha-MSH were detected by RIA in the morning of various days of the cycle. The neurointermediate lobe content of alpha-MSH was slightly elevated on diestrus 1 as compared to the levels on diestrus 11 and proestrus but not to estrous levels. No changes in alpha-MSH content were detected in the anterior pituitary, the median eminence, mediobasal hypothalamus and the preoptic area at various stages of the estrous cycle. Plasma alpha-MSH levels were slightly elevated at 1500 hr of proestrus which was followed three hours later by a decline. This profile of plasma alpha-MSH on the afternoon of proestrus was reproduced by the SC administration of estradiol benzoate to long-term ovariectomized rats. These data suggest that, contrary to the results obtained by bioassay of alpha-MSH no surges of alpha-MSH occur on any day of the cycle, although a slight elevation on the afternoon of proestrus was detected. The altered pattern of release of this peptide on the afternoon of proestrus may be induced by estrogen.

Animals↗

PubMedDate not supplied

The measurement of neuropeptide Y in discrete hypothalamic and limbic regions of male rhesus macaques with a human NPY-directed antiserum.

The distribution of neuropeptide Y (NPY) in microdissected brain regions of male macaques was quantified with a specific radioimmunoassay (RIA). The RIA consisted of a specific antiserum (R31) against human NPY that could detect 7 pg/tube with an IC50 of 125 pg/tube at a final dilution of 1:20,000. Varying amounts of rabbit and monkey mediobasal hypothalami yielded parallel [125I]NPY displacement curves in the assay and similar chromatographic elution profiles with those of synthetic human NPY. The NPY activity in acid extracts of discrete brain regions in castrate and castrated-testosterone-treated rhesus males was highest in mediobasal hypothalamus, followed by more rostral hypothalamic regions and amygdaloid nuclei. Testosterone did not alter NPY levels in any of the brain areas that we examined.

Animals↗

PubMedDate not supplied

Release of hypothalamic neuropeptide Y and effects of exogenous NPY on the release of hypothalamic GnRH and pituitary gonadotropins in intact and ovariectomized does in vitro.

The effect of NPY on the hypothalamic release of GnRH and pituitary release of gonadotropins was examined in intact and ovariectomized (OVEX) rabbits in a superfusion system. Exposure of mediobasal hypothalami (MBH) from intact rabbits to NPY (8 X 10(-8) M) resulted in a sustained stimulation of GnRH secretion into the medium. The same dose of NPY had no effect on MBH-GnRH release from OVEX rabbits. NPY also produced a sustained stimulation of LH and FSH release by pituitary fragments from intact rabbits, but NPY caused only a transient release of these hormones by pituitaries from OVEX does. Media samples from MBH superfusions were also measured for NPY concentrations. NPY was released episodically into the medium. The amplitude and frequency of NPY pulses in intact and OVEX rabbits did not differ; nor were mean levels of NPY significantly affected by castration. These results suggest that NPY has direct effects on both the hypothalamus and pituitary to modulate the the activities of GnRH neurons and gonadotropes. The pattern of GnRH and gonadotropin response to NPY exposure is determined by ovarian factors.

Animals↗