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D R Martinson

Publications and source records attributed to D R Martinson.

11 recordsLinked to original sources
PubMed1995

Dynamics of prolactin secretion from diethylstilbestrol-induced rat prolactinoma tissue in vitro.

Experiments were performed to determine whether PRL secretion in the rat diethylstilbestrol (DES)-induced prolactinoma model is affected by the addition of thyrotropin-releasing hormone (TRH) and/or immunoneutralization of intrapituitary vasoactive intestinal polypeptide (VIP) in vitro. Male Fischer 344 rats were implanted with either a 10 mg DES or placebo pellet 30 days prior to obtaining the anterior pituitary glands for perifusion. The anterior pituitaries were quartered and used in three different perifusion experiments. In Experiment I, placebo-treated tissue channels were perifused for 2 baseline hr followed consecutively by a 30-min exposure to 1:100 nonimmune rabbit serum (NRS), a 30-min wash, and a final 30-min exposure to 10(-5) M TRH. Additional placebo channels were run as above except 1:100 VIP antiserum (AVIP) was substituted for NRS and AVIP was added to the TRH. In Experiment II, the same perifusion protocol was used as in Experiment I, except DES-induced tumor tissue was used instead of placebo tissue. Results from Experiment I and II reveal that AVIP significantly decreased PRL secretory rate in both DES and placebo groups. In the tumor group, both TRH alone and in the presence of AVIP significantly increased the PRL secretory rate. In Experiment III DES-induced tumor tissue channels were perifused with a similar protocol, except the concentrations of NRS and AVIP were increased to 1:10. Both NRS and AVIP significantly decreased PRL secretory rate; however, AVIP had a significantly greater effect than NRS. In this experiment, 1:10 AVIP overcame the stimulatory effect of TRH. In conclusion, AVIP decreases and TRH increases, even in the presence of AVIP, PRL release in DES-induced prolactinoma tissue in vitro. Increasing the AVIP concentration 10-fold diminished the PRL-releasing action of TRH in the tumor tissue. These data suggested that PRL secretion is not autonomous in these prolactinomas and can be affected by exogenous TRH and partial immunoneutralization of endogenous VIP.

Animals↗
PubMed1994

Vasoactive intestinal polypeptide antiserum affects rat prolactin mRNA in 40-day but not 110-day diethylstilbestrol-induced prolactinoma tissue.

Experiments were designed to examine whether vasoactive intestinal polypeptide (VIP), a known stimulator of basal prolactin (PRL) secretion, regulates PRL gene expression in the rat diethylstilbestrol (DES)-induced prolactinoma model. The VIP-induced increase in PRL release could result from increased PRL synthesis and/or decreased PRL degradation. Male Fischer 344 rats were implanted with 10 mg DES pellets 40 or 110 days prior to obtaining the anterior pituitary glands for cell dispersal. Cells were incubated in 1:10 normal rabbit serum or VIP antiserum (AVIP). After incubation, cells were pelleted, washed, and pooled for total nucleic acid extraction. The rat PRL (rPRL) mRNA abundance was quantitated using a solution hybridization/ribonuclease protection assay. Supernatant was collected and analyzed for PRL content using radioimmunoassay. Results from this experiment reveal partial immunoneutralization of intrapituitary VIP significantly decreased PRL secretory rate by rapid reduction in rRPL mRNA in the 40-day tumors. However, in the 110-day tumors the rPRL mRNA steady-state levels were unchanged but the basal release of PRL continued to be decreased by AVIP. These results indicate VIP exerts its effects on PRL secretion through at least two mechanisms.

Animals↗
PubMed1991

Vasoactive intestinal polypeptide and thyrotropin-releasing hormone stimulate newly synthesized, not stored, prolactin.

Experiments were designed to determine whether vasoactive intestinal polypeptide (VIP), reported to stimulate basal PRL secretion, affects PRL processing by lactotrophs. Initially, rat anterior pituitary quarters were incubated for 2 h with [3H]leucine, with and without 10(-5) M VIP, and immunoreactive and immunoprecipitable rPRL were measured during 56 mM KCl perifusion to determine total and 3H-labeled PRL, respectively. Inclusion of VIP increased immunoreactive PRL (P less than 0.05), decreased immunoprecipitable PRL (P less than 0.01), and, therefore, decreased the specific activity of labeled PRL (P less than 0.001). These results suggested an enhanced release of newly synthesized PRL before KCl depolarization, thus decreasing the release of labeled PRL. To discriminate between the two PRL pools, newly synthesized and storage, pituitary quarters were incubated with and without 10(-5) M VIP for 4 h with [14C]leucine, 2 h in cold medium and 2 h with [3H]leucine. Immunoprecipitable PRL was measured during perifusion with 56 mM KCl. Data were depicted as the 3H/14C disintegrations per min ratio of PRL released/3H/14C disintegrations per min of total tissue to account for any differences in tissue labeling. This ratio was greater for tissue labeled in the presence of VIP (P less than 0.002). To determine whether VIP, as a secretagogue, differentiates between the newly synthesized and storage pools, VIP was added after pulse chase, as previously described. No preferential release was observed between the two groups. Finally, using the same [3H]- and [14C]leucine-labeling protocol with and without 10(-5) M VIP, tissue was perifused with medium 199 for 1 h, with 10(-5) M TRH for 30 min, with medium 199 for 30 min, and with 56 mM KCl for 1 h. Inclusion of VIP increased the 3H/14C released/3H/14C total tissue ratio during basal perifusion (P less than 0.04) and TRH exposure (P less than 0.05). Within the control group, the TRH ratio was greater than basal (P less than 0.003). These experiments suggest that newly synthesized PRL is preferentially secreted over stored PRL from tissue incubated with VIP during pulse-chase labeling; however, addition of VIP as a secretagogue did not affect either PRL pool preferentially.

Animals↗
PubMed1986

Antisera to vasoactive intestinal polypeptide inhibit basal prolactin release from dispersed anterior pituitary cells.

Vasoactive intestinal polypeptide (VIP) has been identified in hypothalamic tissue, is secreted into hypophysial portal blood, and stimulates prolactin (PRL) release in vivo and in vitro. It has been proposed, therefore, that VIP is a physiologic PRL-releasing factor. In this study, we confirm that VIP stimulates PRL release from rat pituitary cells in vitro, and demonstrate that an anti-VIP antiserum blocks VIP-induced PRL secretion. Surprisingly, the anti-VIP antiserum inhibited basal PRL secretion from rat pituitary cells in 3 separate experiments. Data from these experiments were pooled, as the responses were similar, revealing basal PRL release of 10.7 +/- 1.3 ng rPRL/10(5) cells (X +/- SE), while anti-VIP antisera significantly inhibited release to 4.4 +/- 0.6 ng rPRL/10(5) cells (p less than 0.001). PRL release in incubates containing control non-immune sera did not differ from basal release, 8.1 ng rPRL/10(5) cells. A further control experiment was conducted wherein cells were incubated with an anti-ACTH antiserum, representing another hyperimmune serum, which had no effect on PRL secretion. These data suggest that VIP, in addition to its possible role as a hypothalamic-derived PRL-releasing factor, may play a role within the pituitary as a regulator of basal PRL secretion.

Animals↗
PubMed1986

Vasoactive intestinal polypeptide is synthesized in anterior pituitary tissue.

Previous studies have suggested that vasoactive intestinal polypeptide (VIP) is involved in regulation of PRL secretion within the pituitary gland. In order to determine whether VIP is synthesized in anterior pituitary tissue, we performed three experiments. In all experiments, anterior pituitaries were obtained from male rats. The tissue was then labeled by incubation in leucine-free minimum essential medium containing [3H]leucine, 14 microCi/ml. In Exp I, the labeled tissue was homogenized, centrifuged, and the supernatant was chromatographed on Sephadex G-50F. The fractions indicated a large peak of counts near the void volume and another peak coeluting with VIP. These latter fractions were pooled and subjected to reverse phase HPLC. Fractions from the HPLC indicated: a protein peak, VIP immunoreactivity, and maximum counts immunoprecipitated by anti-VIP serum at the retention time of synthetic porcine VIP. Exp II consisted of perifusion of labeled pituitary quarters over a 120-min period followed by an additional 60 min in the presence of 56 mM KCl. During this latter period of KCl depolarization, a large amount of 3H-labeled material was secreted. These fractions were then chromatographed on Sephadex G-50F, and the fractions coeluting with [125I]porcine VIP were subjected to immunoprecipitation with anti-VIP serum. In addition, all fractions from the Sephadex column were assayed for VIP, and the only activity was at the elution volume of [125I]porcine VIP. In Exp III, the pituitary labeling procedure included 3.6 X 10(-5) M cycloheximide. Subsequently, the tissue was perifused and the perifusate collected during the 60-min 56 mM KCl perifusion phase was pooled and immunoprecipitated with anti-VIP serum. No immunoprecipitable counts were obtained. These experiments indicate that anterior pituitary tissue synthesizes VIP on the basis of the HPLC profile and immunoprecipitation with specific anti-VIP antiserum. These results, in addition to other studies by our laboratory and others, suggest that intrapituitary VIP may be an important regulator of anterior pituitary hormone secretion, particularly PRL.

Animals↗
PubMed1983

Lack of effect of serotonin and norepinephrine on CRF release from hypothalami in vitro.

A number of investigations utilizing hypothalami from adrenalectomized animals have provided conflicting results regarding the role of serotonin (5HT) and norepinephrine (NE) in CRF regulation. In order to further investigate these neurotransmitters, we performed three sets of experiments with hypothalami obtained from intact rats. In experiment I, freshly obtained rat hypothalami were randomly grouped and incubated in control medium and medium in the presence of 10(-11) M, 10(-10) M, and 10(-9) M serotonin. Aliquots of 200 microliters of these incubates were bioassayed for CRF activity using a dispersed anterior pituitary cell system, and ACTH secretion from the cells was determined by radioimmunoassay. A preliminary experiment had determined that a 200 microliters aliquot from hypothalami incubated in control medium resulted in a significantly (p less than 0.0001) greater ACTH release than obtained from cells alone. No significant effect of serotonin on hypothalamic CRF release was obtained. In experiment III, individual hypothalami were bisected longitudinally, and one half served as control. The contralateral half was incubated in medium containing 10(-11) M, 10(-10) M, and 10(-9) M serotonin. CRF release in this experiment again revealed no significant effect of serotonin. In experiment II, hypothalami were again randomly grouped and incubated with control medium and in the presence of 10(-8) M and 10(-6) M norepinephrine. This experiment resulted in no significant effect of norepinephrine on CRF release. These results suggest that serotonin and norepinephrine at the concentrations studied have no effect on CRF release from hypothalami obtained from intact rats.

Adrenocorticotropic Hormone↗
PubMed1981

Running elevates plasma beta-endorphin immunoreactivity and ACTH in untrained human subjects.

Twenty minutes of submaximal treadmill running was associated with an elevation in plasma levels of beta-endorphin immunoreactivity (P less than 0.02). This increase was greater in men (14.9 +/- 3.4 fmole/ml) than women (2.6 +/- 1.2 fmole/ml)(P less than 0.05). Plasma levels of ACTH and growth hormone also increased after running. ACTH increased more in men (7.8 +/- 1.1 fmole/ml) than in women (1.1 +/-0.44 fmole/ml)(P less than 0.02). There was a similar growth hormone response in both sexes. No correlation can at this time be made with levels in the central nervous system. Changes in plasma levels of beta-endorphin immunoreactivity may be responsible for some of the euphoria and analgesia anecdotally associated with running.

Adrenocorticotropic Hormone↗
PubMed1980

A longitudinal hormonal profile of the genetically obese mouse.

Obese mice (C57BL/6J ob/ob) and their lean littermates were studied at various ages from immediately post weaning until 62 weeks of age, at which mortality increased markedly. Several age-related changes were noted. 1) Plasma glucose levels were elevated in obese mice 5-20 weeks and 62 weeks of age, but were similar to those in the lean mice at 20-60 weeks of age. Plasma insulin levels were elevated in obese mice, and there were no age-related differences. 2) Brain serotonin was elevated in obese mice at all ages and increased with age in both obese and lean animals. 3) Pituitary contents of ACTH and beta-endorphin were elevated in young obese mice and increased further as these mice approached their life expectancy. 4) The ratios of ACTH to beta-endorphin immunoreactivities were similar in obese and lean mice, except in obese mice over 50 weeks of age where this ratio was increased. We conclude that: 1) the obese mouse is characterized by hyperinsulinemia and hyperadrenocorticism throughout its life; 2) the insulin resistance of the obese mouse improves at 20 weeks of age, yet deteriorates as its life expectancy is approached; 3) the obese mouse has an elevated brain serotonin content similar to previously described elevations of the putative neurotransmitters dopamine and norepinephrine in these mice; and 4) as the obese mouse approaches its life expectancy, abnormalities may occur in the synthesis, processing, or secretion of ACTH and/or beta-endorphine.

Adrenocorticotropic Hormone↗
PubMed1975

Effect of glucose on the growth hormone response to L-dopa in normal and diabetic subjects.

The effect of hyperglycemia on the growth hormone response to oral L-dopa (500 mg.) was assessed in eight normal and eight insulin-dependent diabetic subjects. A peak growth hormone response of 21.0 +/- 4.0 ng./ml. (mean +/- S.E.M.), significantly above baseline (p less than 0.01), was achieved in the normal group following oral L-dopa. Glucose concentrations did not change and were approximately 80 mg./100 ml. throughout. Administration of 100 gm. oral glucose with the L-dopa, or thirty minutes thereafter, totally suppressed the growth hormone response in all eight and six of the subjects, respectively. A peak growth hormone response of 20.0 "/- 1.7 ng./ml. (mean +/- S.E.M.), significantly above baseline (p less than 0.001), was obtained in eight nonobese, insulin-dependent diabetics, in spite of prevailing hyperglycemia (mean plasma glucose 243-258 mg./100 ml.) throughout the test. Endogenous hyperglycemia was achieved in these patients by lessening the usual strict adherence to plasma glucose control for the purpose of the study. These results suggest an abnormality in the hypothalamus or pituitary of diabetic subjects allowing growth hormone responsiveness in spite of hyperglycemia.

Adult↗