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Biomedical subjects

A G Frantz

Publications and source records attributed to A G Frantz.

At least 37 records · Page 2Linked to original sources
PubMed1982

Effect of sex steroids on beta-endorphin in hypophyseal portal blood.

Previous studies in female monkeys have shown that beta-endorphin (beta-EP) of hypothalamic origin is present in high concentrations in the hypophyseal portal blood and declines at the time of menses and after ovariectomy. In this study we have examined the effects of estradiol and progesterone replacement on portal blood beta-EP in ovariectomized monkeys. After acute iv administration of estradiol (2 micrograms), beta-EP did not rise from previously low levels (less than 133 pg/ml) over the ensuing 3 h. After chronic estradiol replacement for 3 weeks, portal beta-EP was detectable in 2 of 4 ovariectomized monkeys, with peak values of 341 and 733 pg/ml, respectively. When progesterone as well as estradiol were replaced chronically, high levels of beta-EP, [1610 +/- 192 (SE) pg/ml] were measured in all 13 portal blood samples collected from 4 ovariectomized monkeys. The majority of the beta-EP immunoactivity in these samples eluted from a Sephadex G-50 column in the same position as synthetic human beta-EP. Cation exchange chromatography showed that the majority of immunoactive beta-EP in portal plasma appeared to be nonacetylated beta-EP (1-31). We conclude that ovarian steroids are necessary for the release of hypothalamic beta-EP into portal blood and suggest that cyclic changes in sex steroids may affect anterior pituitary function in part via a mechanism involving hypothalamic beta-EP.

Animals↗
PubMed1981

Dopaminergic and serotonergic involvement in opiate-induced prolactin release in monkeys.

The present experiments were performed to determine the site of action (hypothalamic or hypophyseal) and the mechanism (dopaminergic or serotonergic) by which morphine increases PRL in monkeys (Macaca mulatta and Macaca nemestrina). To determine the site of action, 9 mg morphine were injected iv to four intact and four pituitary stalk-sectioned monkeys. PRL concentrations rose significantly (P less than 0.01) from less than 5 ng/ml to an average maximum value of 208 +/- 20 ng/ml at 15 min in intact animals, but remained unchanged in pituitary stalk-sectioned animals. There was a significant reduction (P less than 0.01) of this response in intact monkeys that received 5 mg L-dopa, iv, 5 min before the morphine stimulus. In these animals, PRL only rose to 100 +/- 46 ng/ml. In contrast, the PRL response in four monkeys pretreated with 5 or 20 mg methysergide, iv (a serotonin receptor blocker), 5 min before the opiate stimulus was not different from in controls. Likewise, the daily administration of 100 mg p-chlorophenylalanine, sc (a serotonin synthesis blocker), for 6 days failed to alter the PRL response to morphine. These data suggest that opiates increase PRL via a neural site of action and that the mechanism may involve dopaminergic but not serotonergic pathways.

Animals↗
PubMed1981

Opioid regulation of prolactin secretion: evidence for a specific role of beta-endorphin.

Previous studies have shown that exogenously administered opioids, including beta-endorphin, stimulate prolactin release. The fact that naloxone has been shown to lower baseline and stress-induced serum prolactin in rats suggests that endogenous opioids may participate in prolactin regulation, but does not specify which opioid is involved. In a previous study we showed that intravenously administered anti-beta-endorphin antiserum had no effect on either baseline or stress-induced prolactin release in rats. In the present study we have repeated our earlier experiments, but have given the antiserum into the cerebral ventricles rather than intravenously. Significant lowering of baseline serum prolactin, to 56.6% +/- 10.6% (SEM) that of controls (p less than 0.005), was noted. Also noted was blunting of the stress-induced prolactin rise, to 69.2% +/- 6.7% that of controls (p less than 0.002). These results indicate that beta-endorphin is specifically involved in both the tonic and stress-mediated release of prolactin. Because the magnitude of prolactin lowering with antiserum was at least as great as what we had earlier observed with naloxone, they suggest that beta-endorphin is the major and possibly the sole opioid involved in prolactin regulation. They also indicate that the previous lack of effect of anti-beta-endorphin antiserum on serum prolactin was due to its failure, after intravenous administration, to achieve effective concentration at critical controlling sites within the brain.

Animals↗
PubMed1981

Human plasma beta-endorphin during pregnancy, labor, and delivery.

beta-Endorphin immunoactivity was measured in the plasma of 50 pregnant women, 25 nonpregnant women, 19 women during labor, and 25 women at the time of vaginal delivery. Simultaneous maternal and umbilical cord plasma samples were obtained in 23 cases. Mean beta-endorphin immunoactivity in the pregnant women was 15.6 +/- 1.6 pg/ml. No significant differences in mean beta-endorphin concentration were found in the first, second, or third trimesters until after the onset of labor, and at no time during this interval did levels differ from the mean of 12 +/- 1.9 pg/ml found in nonpregnant controls. In early labor, beta-endorphin was not elevated (14.8 +/- 2.3 pg/ml), but rose in the later stages of labor (cervical dilatation, > 4 cm) to 70.3 +/- 8.2 pg/ml and peaked during delivery at 113 +/- 13.3 pg/ml. Chromatography of plasma from women at delivery, pregnant women not in labor, and nonpregnant controls to separate beta-endorphin from cross-reacting beta-lipotropin showed mean beta-endorphin to beta-lipotropin molar ratios of 0.22-0.27 in the three groups, with no significant differences among the groups. In 23 subjects in whom simultaneous maternal and umbilical cord plasma samples were obtained, there was no correlation between the beta-endorphin immunoactivity in the paired samples, supporting the concept that fetal beta-endorphin is not of maternal origin. In 13 fetal umbilical cord samples, ACTH was measured in addition to beta-endorphin immunoactivity. A close correlation (r = 0.836) was observed between the concentrations of the two peptides, suggesting that in the fetus, as in the adult, beta-endorphin and ACTH are processed in parallel from a common precursor.

Adolescent↗
PubMed1980

Section of the pituitary stalk in the rhesus monkey. I. Endocrine studies.

The effects of pituitary stalk section on anterior pituitary secretion were studied in 20 female rhesus monkeys. Vascular connections between the hypothalamus and the pituitary gland were permanently interrupted in all but 4 animals. Prolactin levels rose rapidly and remained significantly elevated in all effectively stalk-sectioned animals for as long as the observation period (up to 3 years). Only smaller and transient elevations of prolactin were seen in the animals in which revascularization of the anterior pituitary gland had occurred. Growth hormone and cortisol were significantly decreased after stalk section, and were not released by insulin. Radioimmunoassayable luteinizing hormone (LH) levels decreased following surgery and, by bioassay, LH became undetectable within 5 weeks after stalk section, indicating that gonadotropin-releasing hormone is essential for the viability of the gonadotrope. The results indicate that plasma prolactin concentrations can be used to monitor completeness of pituitary gland isolation from direct hypothalamic influence. Stalk-sectioned monkeys provide good models to study direct pituitary effects of various hormones or drugs.

Animals↗
PubMed1980

Effects of substance P on anterior pituitary secretion in the female rhesus monkey.

The effects of substance P on anterior pituitary secretion were studied in 3 female rhesus monkeys. In nine experiments, 100 microgram substance P was injected intraventricularly, and the results were compared to those obtained following intraventricular injection of the control vehicle. In 7 out of 9 experiments, substance P induced a significant increase in prolactin secretion within 5 min. Peak levels at 10 min were approximately 15-20 times those of the baseline control. Substance P also induced a slight but significant decrease in GH secretion 20 min following injection, but at other times GH levels were not significantly changed. LH and FSH as well as cortisol concentrations remained unaltered. In 2 monkeys a decrease in systolic pressure of 40-70 mm Hg within 10-60 sec and lasting 180-300 sec was observed following the administration of substance P but not the control vehicle. The results indicate that substance P, which in the monkey has been shown to be associated with hypothalamic regions implicated in the control of anterior pituitary secretion, can alter prolactin and GH release.

Animals↗
PubMed1980

High levels of beta-endorphin in hypophyseal portal blood.

beta-Endorphin was measured by RIA in the hypophyseal portal blood of six pig tailed monkeys after pituitary stalk section. The mean beta-endorphin concentration was 4,770 pg/ml (range, 2,900-10,500 pg/ml). This was more than 100 times greater than the mean simultaneous peripheral venous concentration, which was less than or equal to 45 pg/ml. After gel filtration of the portal plasma extracts, the majority of beta-endorphin immunoactivity eluted as a single peak coincident with synthetic beta-endorphin standard. The demonstration of high levels of beta-endorphin in the hypophyseal portal blood suggests that endogenous opioids of hypothalamic origin are secreted into the portal blood and may directly affect the pituitary.

Animals↗
PubMed1980

Effect of estrogen on thyrotropin-releasing hormone-induced release of prolactin in intact, ovariectomized, and stalk-sectioned female rhesus monkeys.

The effects of estrogen treatment on basal and TRH-induced serum PRL concentrations were studied in three groups of four female rhesus monkeys; intact monkeys, ovariectomized animals, and monkeys in which the pituitary gland had been isolated from direct hypothalamic influences by pituitary stalk section. The TRH tests (50 microgram, iv) were performed before and 7 and 21 days after the sc implantation of one or two 3-cm long silastic capsules containing 17 beta-estradiol. Treatment with estradiol significantly increased the PRL response to TRH in the three groups of animals. The highest PRL response to TRH was observed after stalk section. The estrogen treatment also increased basal PRL concentrations in stalk-sectioned monkeys but no statistically significant increase was observed in intact or ovariectomized animals. These results indicate that physiological amounts of estradiol increase the magnitude of TRH-induced PRL release in rhesus monkeys, and that this estrogen effect is probably enacted directly at the level of the anterior pituitary gland.

Animals↗
PubMed1980

Failure of beta-endorphin to stimulate prolactin release in the pituitary stalk-sectioned monkey.

To study the locus at which opioids act to release PRL in vivo, beta-endorphin (beta-EP) was injected into intact and pituitary stalk-sectioned monkeys. In each of five intact monkeys, serum PRL rose to peak concentrations of 200-300% of baseline 20 min after injection. In contrast, beta-EP failed to cause any PRL increase in four stalk-sectioned animals. Beta-EP also failed to stimulate PRL in two stalk-sectioned monkeys receiving estrogen replacement, indicating that estrogen deficiency was not the cause of their failure to respond. To test possible antagonism of dopamine by beta-EP directly at the pituitary, L-dopa was given to six stalk-sectioned monkeys with and without beta-EP pretreatment. No alteration of the PRL suppression by L-dopa was observed Disappearance of injected beta-EP from plasma was studied in four intact monkeys. Initial and terminal half-lives ranged from 2.3-4.0 min and from 16.0-30.2 min, respectively; MCRs ranged from 70-170 ml/min. We conclude that beta-EP does not stimulate PRL secretion either directly or by interacting with dopamine at the pituitary level. These results support a hypothalamic rather than a direct pituitary site of action for opioid-stimulated PRL release.

Animals↗
PubMed1980

The effects of serotonin on prolactin and growth hormone concentrations in normal and pituitary stalk-sectioned monkeys.

The effects of serotonin on PRL and GH secretion were studied in normal and pituitary stalk-sectioned female rhesus monkeys. Serotonin was administered iv at doses of 50, 500, 5000 microgram. Pretreatment concentrations of serum PRL were elevated in stalk-sectioned monkeys compared to normal monkeys [34 +/- 5 vs. 3 +/- 1 ng/ml (mean +/- SEM)], while serum GH concentrations were lower in the stalk-sectioned animals (< 0.5 vs. 1.3 +/- 0.2 ng/ml). In both normal and stalk-sectioned monkeys, the 5-microgram dose of serotonin failed to alter PRL concentrations. However, with the 500-microgram dose, PRL rose from 3 +/- 1 to 22 +/- 6 ng/ml in normal monkeys and from 27 +/- 6 to 57 +/- 10 ng/ml in stalk-sectioned monkeys. Likewise, with the 5000-microgram dose, PRL rose from 4 +/- 2 to 82 +/- 27 and from 30 +/- 6 to 75 +/- 26 ng/ml in the two respective groups. No dose of serotonin stimulated GH secretion in stalk-sectioned monkeys, although GH did increase from approximately 2 to 4-11 ng/ml in normal monkeys. Since the pituitary is devoid of direct hypothalamic influences in the pituitary stalk-sectioned animals, these results suggest that serotonin can modulate PRL secretion either directly at the pituitary level or via some yet to be determined peripheral mechanism. In contrast, this neurotransmitter appears to incorporate hypothalamic factors in its modulation of GH secretion.

Animals↗
PubMed1979

Measurement of beta-endorphin in human plasma.

beta-endorphin has been identified in human plasma by means of gel filtration and a sensitive radioimmunoassay for human beta-endorphin (beta h-endorphin). Mean baseline plasma beta h-endorphin concentration in 5 individuals was 21 +/- 7.3 (SD) pg/ml (6.2 +/- 2.2 (SD) fmole/ml). Following metyrapone stimulation mean plasma concentration increased to 55.4 +/- 10.1 (SD) pg/ml (16.3 +/- 3.1 (SD) fmole/ml). The molar ratio of human beta-lipotropin (beta h-LPH) to beta h-endorphin was 2.2 in baseline plasma and 2.4 after metyrapone stimulation.

Chromatography, Gel↗
PubMed1979

Ectopic human growth hormone in ovaries and breast cancer.

Immunoreactive human GH (hGH) has been found in 8 of 118 surgically removed ovaries, with concentrations ranging from 50-51,000 ng/g tissue. The highest concentration was in an ovarian metastasis from an adenocarcinoma of the breast; a skin metastasis from this same carcinoma had an hGH concentration of 350,000 ng/g. All specimens were positive for hGH by radioreceptor assay as well as by RIA. Examination of four specimens at multiple dilutions by lactogenic and somatotropic receptor assays as well as by RIA did not reveal significant differences in slope between these specimens and that of the hGH standard. Sephadex gel chromatography of two specimens showed the major peak of immunoactivity eluting coincident with monomeric hGH. Ectopic hGH has not previously been reported in ovary or breast.

Breast Neoplasms↗