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N Ben-Jonathan

Publications and source records attributed to N Ben-Jonathan.

At least 73 records · Page 4Linked to original sources

The rat posterior pituitary contains a potent prolactin-releasing factor: studies with perifused anterior pituitary cells.

UNLABELLED: We previously reported that removal of the posterior pituitary abolished the suckling-induced rise in plasma PRL. This suggested that the posterior pituitary contains a PRL-releasing factor (PRF). Using perifused anterior pituitary cells, the objectives of this study were 1) to examine whether the posterior pituitary contains PRF activity as compared to the medial basal hypothalamus (MBH), and 2) to determine to what extent substances known to be present in the posterior pituitary and/or MBH contribute to this activity. Anterior pituitary cells, attached to Cytodex beads, were perifused with medium 199. Tissues were extracted with acid, lyophilized, and reconstituted in medium 199. Tissue extracts and synthetic compounds were introduced to the cells in short pulses. Fractions were collected and analyzed for PRL, LH, and GH by RIA. Posterior pituitary extracts contained a potent substance(s) which stimulated PRL release in a concentration-dependent manner, but did not alter LH secretion. As little as 1% of the extract increased PRL release. In contrast, the MBH extract contained significantly less PRF activity but was capable of stimulating and inhibiting LH and GH release, respectively. Cerebellar extracts did not alter PRL secretion. Of more than 25 neuroactive substances tested in the perifusion system, oxytocin, TRH, and angiotensin II (A II) appeared as likely candidates for PRF. Therefore, the specific receptor antagonists d(CH2)5Tyr(Me) ornithine vasotocin (for oxytocin), chlordiazepoxide (for TRH), or saralasin (for A II) were infused together with the posterior pituitary extract. These antagonists completely abolished the PRL-releasing activities of their respective peptides but failed to reduce the PRF activity of the posterior pituitary. In contrast, PRF activity in the MBH was nearly eliminated by the TRH antagonist. CONCLUSIONS: 1) The rat posterior pituitary contains a potent PRF capable of inducing a rapid, hormone-specific, concentration-dependent stimulation of PRL release from perifused anterior pituitary cells. 2) The MBH contains significantly less PRF activity, which is largely attributable to TRH. 3) Although the chemical identity of PRF is yet unknown, the PRF activity in the posterior pituitary is not accounted for by oxytocin, TRH, or A II.

Angiotensin II↗

Catecholamine content of the preovulatory follicles of the domestic hen.

The role of catecholamines in ovarian function of the domestic hen has not been examined extensively. The aim of this study was first to determine the location of catecholamines in the preovulatory follicle of the domestic hen. Second, norepinephrine (NE), epinephrine (EPI) and dopamine (DA) were measured in the isolated theca layer of the five largest preovulatory follicles at specific times during the ovulatory cycle and changes in catecholamine content were correlated with ovarian events. The five largest preovulatory follicles were removed from chickens at 24, 18, 12, 6 and 2 h before ovulation of the largest (F1) follicle. Theca and granulosa layers were isolated, frozen, weighed and prepared for measurements of catecholamines by the double isotope radio-enzymatic assay. Catecholamines were localized primarily in the theca layer with only small amounts present in the granulosa layer. Norepinephrine was present in the theca layer in concentrations 6- and 30-fold those of EPI and DA, respectively. The content of NE and EPI in the theca layer of the F1 follicle was significantly (p less than 0.01) higher at 6 h before ovulation than at other times for the F1 follicle. In contrast, NE and EPI content of the theca layer of second (F2) and third (F3) largest follicles did not change during the ovulatory cycle. The content of DA was elevated (p less than 0.05) at 12 h before ovulation in F1 and F2 follicles. There was a significant reduction in NE in the theca layer of the fifth largest (F5) follicle between 24 and 18 h before ovulation of the F1 follicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Chronic posterior pituitary lobectomy: prolonged elevation of plasma prolactin and interruption of cyclicity.

We previously reported that the posterior pituitary dopaminergic system participates in the inhibition of prolactin (PRL) secretion in both male and lactating female rats. However, posterior pituitary lobectomy (Lobex) of urethane-anesthetized cycling rats resulted in an elevation in plasma PRL for a short time only. This raises a question regarding the importance of input from the posterior pituitary to the control of PRL secretion during the estrous cycle. The objectives of this study were to examine the chronic effects of Lobex on plasma PRL levels in conscious rats and to determine whether the absence of input from the posterior pituitary interferes with estrous cyclicity. Lobex or sham lobectomy were performed under Brevital anesthesia in estrous rats. Blood was collected from jugular cannula at hourly intervals on the day of surgery and at 09.00, 13.00, and 17.00 h during the following 4 days. Daily water consumption and vaginal cyclicity were monitored for 14 and 20 days, respectively. Within 2 h after Lobex, the plasma PRL levels rose 3- to 4-fold and remained elevated for 3 days before declining to near control levels on the 4th day. None of the Lobex rats resumed cyclicity within 3-4 days, 50% had an interruption of cyclicity for 4-10 days, and the remainder were noncyclic for more than 11 days. Upon resumption of cyclicity, Lobex rats had 11.3 +/- 0.4 oviductal ova which is within the normal range for intact ovulating rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distribution of catecholamines between fetal and maternal compartments during human pregnancy with emphasis on L-dopa and dopamine.

This study was undertaken to determine the differential distribution of catecholamines, in particular L-dihydroxyphenylalanine (L-dopa) and dopamine, between the fetal and maternal compartments during human pregnancy. Amniotic fluid and fetal and maternal blood were obtained from two groups of pregnant women with uncomplicated pregnancies. One group was at 15-20 weeks of gestation and the second group was in labor after 36-41 weeks of gestation. Samples were analyzed for L-dopa, dopamine, norepinephrine, and epinephrine by radioenzymatic assays. L-Dopa constituted about 80% of the total circulating fetal catecholamines, and levels were 2- to 3-fold higher in fetal than maternal plasma. Marked increases in norepinephrine, small rises in epinephrine, but no changes in L-dopa or dopamine concentrations occurred in fetal plasma from mid- to late gestation. Maternal plasma catecholamines did not change. Towards the end of gestation, dopamine in the amniotic fluid increased 15-fold, and norepinephrine increased 5- to 6-fold; L-dopa remained high and unchanged. We conclude that L-dopa is the predominant catecholamine in fetal plasma and amniotic fluid during human pregnancy. No significant changes in its concentrations occur in either compartment between mid- and late gestation. In contrast, dopamine levels, which are 30- to 50-fold lower than those of L-dopa in amniotic fluid during midgestation, show a striking elevation toward the time of labor. Neither the sources nor the possible physiological functions of either L-dopa or dopamine during fetal life are known.

Amniotic Fluid↗

Interaction between the posterior pituitary and LHRH in the control of LH secretion.

We have recently reported that the posterior lobe of the pituitary differentially inhibits the secretion of prolactin (PRL) and luteinizing hormone (LH), but not follicle stimulating hormone (FSH) throughout the estrous cycle. Removal of the posterior pituitary (posterior pituitary lobectomy) results in elevations of plasma LH on all days of the cycle except on diestrus-day-2. In the present study we examined: whether the control of LH release involves an interaction between the posterior pituitary and hypothalamic luteinizing hormone-releasing hormone (LHRH), and whether the elevation of LH seen following posterior lobectomy is due to the removal of a posterior pituitary substance(s) which alters anterior pituitary sensitivity to LHRH. In order to block the action of hypothalamic LHRH, a potent LHRH inhibitory analog (50 micrograms) was injected SC two hours prior to removal of the posterior pituitary in estrous rats. Administration of the inhibitory analog completely eliminated the elevation of plasma LH seen following posterior lobectomy, but did not alter the posterior lobectomy-induced rise of plasma PRL, or plasma FSH concentrations. In order to test whether anterior pituitary sensitivity to LHRH is altered by posterior lobectomy, a moderate dose of LHRH (15 ng) was administered to both posterior lobectomized and sham lobectomized estrous rats. The time-course and magnitude of the LH response to LHRH was similar in both groups. The results are consistent with the hypothesis that LH secretion is controlled by an interaction between hypothalamic LHRH and the posterior lobe of the pituitary, but this interaction does not appear to involve lobectomy-induced changes in anterior pituitary responsiveness to LHRH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Elevated catecholamines in porcine follicular fluid before ovulation.

The purpose of this study was to correlate changes in catecholamine concentrations in porcine follicular fluid and cyclic events in the ovary. Follicular fluid was aspirated from follicles of ovaries obtained from pigs throughout the 21-day estrous cycle and analyzed for norepinephrine (NE), epinephrine (EPI), and estradiol (E2). Serum was obtained from cycling pigs on days 6-10 and 16-20 of the cycle and assayed for NE, EPI, E2, and progesterone. The concentrations of NE in the follicular fluid were relatively constant during days 1-15 of the luteal phase (1.7 +/- 0.2 ng/ml), but were elevated significantly to 2.9 +/- 0.4 ng/ml during the follicular phase (days 16-20). EPI had a similar profile, but a 6- to 10-fold lower concentration. The follicular fluid E2 concentration increased from 15.6 to 76.5 ng/ml during the luteal phase to 630 ng/ml during the follicular phase. Serum NE and EPI concentrations were similar during midluteal and follicular phases, whereas progesterone and E2 were significantly elevated during the luteal and follicular phases, respectively. These results indicate that catecholamines in follicular fluid are elevated significantly during the follicular phase of the estrous cycle and may have a physiological role in preovulatory events as well as during the luteinization process.

Animals↗

Predominance of L-dopa in fetal plasma and the amniotic fluid during late gestation in the rat.

The purpose of this study was to reevaluate catecholamine distribution in fetal and maternal compartments during late gestation in the rat. Fetal and maternal plasma and amniotic fluid were collected from anesthetized rats on consecutive days from day 17 to day 22, the day of parturition. The fluid was analyzed for dihydroxyphenylalanine (L-dopa), dopamine, norepinephrine, and epinephrine by radioenzymatic assays. Amniotic fluid volume was determined by a direct weighing method. L-Dopa concentrations constituted approximately 50% of total fetal plasma catecholamines and were significantly higher in fetal than in maternal circulation. Dopamine concentrations in fetal plasma were tenfold lower than those of L-dopa but were also significantly higher in fetal than in maternal plasma; norepinephrine levels were similar in both. Maternal plasma epinephrine levels remained relatively constant, whereas fetal epinephrine levels increased fiftyfold from day 17 to day 22. L-Dopa concentrations in the amniotic fluid were tenfold higher than those of dopamine, and the concentrations of both increased markedly during the last 2 days of gestation. However, this apparent rise could be attributed to the concomitant fivefold reduction in the amniotic fluid volume observed at this time. It is concluded that L-dopa is the predominant catecholamine in both the fetal plasma and the amniotic fluid during late gestation in the rat. At the present time, neither the source nor the possible physiologic functions of L-dopa during fetal life are known.

Amniotic Fluid↗

Prolactin secretion by cultured anterior pituitary cells: influence of culture conditions and endocrine status of the pituitary donor.

The characteristics of prolactin (PRL) secretion by cultured anterior pituitary cells in the presence and absence of catecholamines were studied. PRL secretion was markedly influenced by culture conditions such as cell density, culture duration and length of short-term incubation. Dopamine (DA) inhibited PRL release in a dose-dependent manner within a physiological range, and this inhibition was reversed by the stereospecific DA receptor antagonist (+)-butaclamol. In contrast, the inhibition of PRL secretion by norepinephrine (NE) required much higher doses and lacked specificity. Cells obtained from male donors had the lowest basal PRL secretion and were the least responsive to DA inhibition, whereas those obtained from females in late pregnancy had the highest basal PRL secretion and were the most sensitive to DA.

Animals↗

Posterior pituitary involvement in the control of luteinizing hormone and prolactin secretion during the estrous cycle.

The effects of removal of the posterior lobe of the pituitary on plasma concentrations of PRL, LH, and FSH were examined under the following conditions: on each morning of the 4-day estrous cycle, 2 weeks after ovariectomy, and 2 h after the administration of a LHRH inhibitory analog on estrus. Blood was collected from a femoral artery immediately before and during the 3 h after posterior pituitary lobectomy or sham lobectomy. Significant elevations of both PRL and LH were seen after removal of the posterior pituitary on estrus and diestrus day 1, while no change was seen in the plasma concentration of either hormone after posterior pituitary removal on diestrus day 2. On proestrus, posterior lobectomy resulted in an elevation of LH only. The posterior lobectomy-induced PRL elevations were rapid and of short duration, while those of LH were delayed and prolonged. No alteration in plasma FSH concentrations was seen after posterior pituitary lobectomy performed on any day of the estrous cycle. In contrast to the hormonal elevations observed after lobectomy during the cycle, no change in plasma PRL, LH, or FSH was seen after posterior lobectomy in ovariectomized rats. The administration of a LHRH inhibitory analog 2 h before posterior lobectomy completely abolished the lobectomy-induced rise of LH normally seen on estrus. The data suggest that the posterior pituitary participates in the regulation of PRL and LH, but not FSH, release during the estrous cycle. Given that the posterior lobectomy-induced elevations of plasma PRL and LH were evident only on certain days of the cycle and were absent in ovariectomized rats, it is likely that posterior pituitary inhibition of PRL and LH release is expressed only in the presence of specific ovarian hormonal profiles. In addition, the posterior lobectomy-induced rise in plasma LH appears to be dependent on the presence of LHRH, but it remains to be determined whether a posterior pituitary substance(s) alters hypothalamic release of or anterior pituitary responsiveness to LHRH.

Animals↗

Norepinephrine in the rat ovary: ontogeny and de novo synthesis.

The aims of this study were to characterize the ontogeny of catecholamines (CA) in the rat ovary, to determine the ability of the immature ovary to synthetize norepinephrine (NE) in vitro, and to correlate between ovarian CA and plasma pituitary hormones. Ovaries, spleen (as a control tissue not subjected to endocrine regulation), and trunk blood were collected at 5-day intervals between days 5 and 40. Ovarian NE concentration increased markedly between days 20 and 35 of life, whereas the major rise in splenic NE concentration occurred between days 10 and 15. Ovarian and splenic tissues from neonatal females were capable of de novo synthesis of NE from tritiated tyrosine without an appreciable accumulation of L-Dopa and dopamine. The rate of NE synthesis by ovarian tissue taken from 20-day-old rats was significantly lower than that from 30- and 40-day-old rats, whereas NE production by splenic tissue from 20-, 30-, and 40-day-old rats were similar. Plasma FSH concentration was significantly elevated between days 10 and 20, whereas the major rise in plasma LH and PRL occurred between days 25 and 40. The following conclusions were reached. The delayed elevation of ovarian NE, compared to splenic NE, is attributable to a decreased production of NE by the ovary on day 20 and may involve a suppression or a delay in development of the activity of a key CA biosynthetic enzyme such as tyrosine hydroxylase. Given the temporal relationship between plasma gonadotropins, in particular FSH, and changes in ovarian NE, it is postulated that ovarian CA during neonatal development are subjected to regulation by circulating pituitary hormones.

Animals↗

Increase in pituitary dopaminergic receptors after monosodium glutamate treatment.

We investigated whether a decrease in arcuate nucleus dopamine (DA) levels resulting from neonatal treatment with monosodium glutamate (MSG) affects the anterior pituitary DA receptors in adult male rats. MSG treatment resulted in a significant reduction in medial basal hypothalamic (MBH) DA levels, no change in its norepinephrine (NE) and epinephrine (E) concentrations, and a marked increase in circulating prolactin (PRL). Scatchard analyses of DA binding characteristics to anterior pituitary membranes using [3H]spiperone revealed linear plots, suggesting a single class of high-affinity, low-capacity binding sites. The DA binding capacity was significantly higher in MSG-treated rats than in controls with no change in affinity. The data indicate that anterior pituitary DA receptors change in accordance with altered physiological conditions. The increase in the number of DA receptors following destruction of the arcuate nucleus is probably a direct effect of reduced DA levels reaching the anterior pituitary gland.

Animals↗

Plasma catecholamines in the chronically cannulated sheep fetus: predominance of L-dihydroxyphenylalanine.

Dihydroxyphenylalanine (Dopa) and catecholamines (CA) concentrations were determined in plasma collected from chronically cannulated fetal and maternal sheep from days 125-140 of gestation. Dopa was measured by a radioenzymatic assay, followed by ion exchange chromatography and high performance liquid chromatography. The assay was linear to 2.5 ng Dopa, and its sensitivity was 35-45 pg. Dopamine (DA), norepinephrine, and epinephrine were determined simultaneously by the same radioenzymatic incubation procedure, followed by solvent extraction and two-dimensional thin layer chromatography. The Dopa level in the fetal circulation was 10-25 times higher than that of DA, 5-10 times higher than that of norepinephrine, and 100 times higher than that of epinephrine. Furthermore, Dopa was the only CA that was significantly (P less than 0.05) higher in fetal (3.5-4.5 ng/ml) than in maternal plasma (1-1.5 ng/ml). The data indicate that Dopa is the predominant circulating CA in the sheep fetus. While the physiological importance of this observation is unknown at the present time, fetal Dopa might serve as the source of free DA in fetal urine and/or amniotic fluid.

Animals↗

Norepinephrine in Graafian follicles is depleted by follicle-stimulating hormone.

The purpose of the present study was to measure norepinephrine (NE) in Graafian follicles and correlate changes in its concentration with circulating gonadotropins secreted endogenously or administered exogenously. Graafian follicles were removed from the ovaries of adult cycling rats. The follicles were pooled in groups of 10-13, and NE was determined by high performance liquid chromatography. Follicular NE(picograms per micrograms protein) did not change between 0900 h (3.61 +/- 0.34) and 1300 h (3.12 +/- 0.25) on proestrus, but was reduced significantly to 1.45 +/- 0.16 at 2100 h, which is 4 h after the peak of the gonadotropin surge. There was a further reduction to 0.83 +/- 0.08 in fresh corpora lutea taken on estrus at 0900 h. The decrease in follicular NE was prevented in estrous rats which were either hypophysectomized 24 h previously or treated with sodium pentobarbital at 1330 h on proestrus. To determine which pituitary hormone was responsible for follicular NE depletion, rats were injected at 0900 h on proestrus with LH (5 micrograms), FSH (20 micrograms), LH plus FSH (5 and 20 micrograms, respectively), or PRL (20 micrograms), and follicular NE was determined 4 h later. FSH reduced follicular NE significantly to 1.86 +/- 0.16 compared to both the control (3.12 +/- 0.25) and the PRL-injected group (2.92 +/- 0.32), whereas LH caused a small but nonsignificant decrease (2.49 +/- 0.2). Both LH and FSH doses used resulted in ovulation, as determined by counting tubal ova 12 h after hormonal treatment. We conclude that 1) NE in Graafian follicles is markedly reduced within 4 h after the preovulatory gonadotropin surge in the normal cycling rat; this reduction is prevented when the surge is abolished; 2) the hormone responsible for follicular NE depletion is FSH rather than LH or PRL; and 3) finally, it is suggested that follicular NE may be involved with the formation and/or functioning of the corpus luteum.

Animals↗

Posterior pituitary lobectomy: differential elevation of plasma prolactin and luteinizing hormone in estrous and lactating rats.

The effects of posterior pituitary lobectomy on PRL and LH secretion in estrous and lactating rats were examined. Blood was collected from a femoral artery immediately before and at various times after the removal of the posterior lobe from anesthetized rats. Rats in estrus were also subjected to chronic posterior lobectomy, and their water consumption and vaginal cytology were determined for 3 weeks. Within 5--10 min after posterior lobectomy in estrous rats, plasma PRL increased 3-fold, but declined to near control levels by 1--2 h. Plasma LH increased more gradually, reaching 4 times the control level after 2--3 h. No change was observed in plasma GH. Injection of dopamine to posterior lobectomized estrous rats caused an immediate fall in plasma PRL, but no change in LH. Plasma PRL in lactating rats increased 4-fold after posterior lobectomy, reaching a peak concentration by 30 min and remaining elevated for at least 3 h; plasma LH was unchanged. Eighty percent of chronic posterior lobectomized rats became pseudopregnant and then resumed normal cyclicity. Water consumption increased 3-fold after posterior lobectomy, but declined to 60--70% above the control level after 2--3 weeks. The data suggest that the posterior lobe participates in the regulation of PRL secretion via a dopaminergic mechanism; such regulation might be more pronounced during lactation than in estrus. In addition, the posterior pituitary appears to contribute to the regulation of LH secretion during estrus. The factor(s) of posterior pituitary origin responsible for inhibiting LH secretion is unknown at the present time.

Animals↗

Dopaminergic receptors in the rat anterior pituitary change during the estrous cycle.

We investigated whether rat anterior pituitary dopaminergic receptors change in affinity and/or number of binding sites (Bmax) during the estrous cycle and whether they correlate with circulating PRL levels. Dopamine receptors were quantitated in partially purified pituitary membranes by equilibrium binding using [3H]spiperone. AT 0900 h of diestrous day 2 and 0900 h of proestrus, Bmax [316.5 +/- 7.7 and 297.9 +/- 7.3 fmol/mg protein (mean +/- SE), respectively] and plasma PRL levels (18.2 +/- 4.2 and 25.0 +/- 7.3 ng/ml, respectively) were low. Bmax remained low (305.6 +/- 22.1 fmol/mg) at 1300 h of proestrus, but PRL increased 5-fold. At 1700 h of proestrus, Bmax significantly increased to 453.3 +/- 27.2 fmol/mg, coincident with a preovulatory PRL surge (241.5 +/- 45.4 ng/ml). By 0900 h of estrus, Bmax decreased to 389.5 +/- 20.1 fmol/mg and did not return to basal levels until diestrous day 2. PRL also decreased by 0900 h of estrus to 106.6 +/- 13.0 ng/ml and progressively fell to basal level by 0900 h of diestrous day 1. Receptor affinity was unchanged throughout the cycle (range, 0.08-0.15 nM). These data indicate that the number of dopaminergic binding sides changes significantly during the estrous cycle, with the sharpest increase in the afternoon of proestrus. Since a complex relationship is apparent between alterations in dopaminergic receptor number and plasma PRL levels, we postulate that these receptors may be regulated by dopamine, ovarian steroids, and/or PRL itself. Such a change in the number of dopaminergic binding sites may e an important component in pituitary responsiveness to dopamine inhibition of PRL secretion throughout the estrous cycle.

Animals↗