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D M Lawson

Publications and source records attributed to D M Lawson.

At least 73 records · Page 4Linked to original sources
PubMed1986

The effects of transient dopamine antagonism on thyrotropin-releasing hormone-induced prolactin release in pseudopregnant rats.

The effectiveness of TRH in releasing PRL after transient dopamine (DA) blockade was investigated in female rats between days 3 and 11 of pseudopregnancy (PSP). At 0930 h on the morning of the experiment, each animal was injected with the DA antagonist domperidone (0.01 mg/rat, iv) or vehicle (acetic acid in saline); 5 min later, the DA agonist 2-bromo-alpha-ergocryptine maleate (CB-154; 0.5 mg/rat, iv) was administered. Sixty minutes later, TRH (1.0 micrograms/rat, iv) was administered. Blood samples were withdrawn via indwelling catheters before, 5, 20, 40, and 70 min after domperidone or vehicle administration, and 5 and 10 min after TRH administration. On day 3 of PSP, TRH-induced PRL release was significantly enhanced by the domperidone-CB154 treatment compared to that in vehicle-treated control rats. By day 9 of PSP, the effectiveness of TRH in stimulating PRL release after domperidone treatment was decreased by 50% compared to that on day 3 of PSP. This reduction in PRL response to TRH was not due to decreased progesterone levels, as no difference was observed in plasma progesterone between days 3 and 9. Rats that were given domperidone on day 11 of PSP did not exhibit a significant increase in sensitivity to TRH; however, the effectiveness of TRH was enhanced by domperidone on day 11 of PSP in animals that were hysterectomized on day 2 of PSP. Since DA receptor blockage increased the sensitivity to a putative PRL-releasing factor (TRH) and this mechanism was eliminated around the time that the PRL surges of PSP disappear, we suggest that this pituitary mechanism is a critical component of the PRL release mechanism during the surges of PSP. Further, the observed loss of the mechanism between days 9 and 11 of PSP may be due to the direct influence at the anterior pituitary of a uterine PRL inhibitory factor which has been recently described.

Animals↗
PubMed1986

The effect of transient dopamine antagonism on thyrotropin-releasing hormone-induced prolactin release in ovariectomized rats treated with estradiol and/or progesterone.

PRL release was studied in ovariectomized (OVX) rats pretreated with estradiol benzoate (EB), progesterone (P), or a combination of both steroids using a protocol that was selected to mimic ovarian steroid changes that have been observed during the female rat 4-day estrous cycle and early pregnancy. On the morning of the experiment, the animals received injections of either the dopamine (DA) antagonist domperidone (0.01 mg/rat iv) or vehicle (acetic acid in saline). Five minutes later, all animals received injections of the DA agonist 2-bromo-alpha-ergocryptine (CB-154; 0.5 mg/rat, iv) followed 60 min later by the administration of TRH (1.0 microgram/rat, iv). Plasma obtained from blood samples taken during the experiment was assayed for PRL by RIA. In OVX or P-treated OVX rats, a transient blockade of DA by domperidone did not alter the sensitivity of the pituitary to TRH administration, as measured by an increase in plasma PRL. However, such an effect of DA blockade was induced by 2 days of EB treatment and was maintained and amplified by P administration after EB injections. We conclude that enhancement of the PRL-releasing effect of TRH by DA antagonism, a mechanism we previously observed in female rats during midlactation, proestrus, estrus, and metestrus using the present drug protocol, can be induced by estrogen and maintained by P. Further, our data suggest that the previously observed loss of this secretory mechanism on the morning of diestrus may be due to the decrease in plasma P that takes place between metestrus and diestrus.

Animals↗
PubMed1985

Prolactin stimulation of Nb 2 node lymphoma cell division is inhibited by polyamine biosynthesis inhibitors.

The mitogenic action of prolactin in Nb 2 node lymphoma cells was inhibited by two drugs which interfere with polyamine biosynthesis. At concentrations of 0.5 mM and above alpha-difluoromethyl ornithine (DFMO), which inhibits ornithine decarboxylase and the conversion of ornithine to putrescine, significantly attenuated the mitogenic effect of prolactin. This inhibition was prevented by the addition of putrescine, spermidine, or spermine to the culture medium. At concentrations of 1 microM and above methylglyoxal bis(guanylhydrazone) (MGBG), which inhibits S-adenosylmethionine decarboxylase and hence the conversion of putrescine to spermidine and spermine, abolished the mitogenic action of prolactin. This inhibition was prevented by the addition of spermidine or spermine, but not putrescine, to the culture medium. These studies show that ongoing polyamine biosynthesis is essential for prolactin to express its mitogenic effect in this lymphoma cell line.

Adenosylmethionine Decarboxylase↗
PubMed1984

Ovariectomized Sprague-Dawley and Long-Evans rats release prolactin differently in response to estrogen.

Mature female Sprague-Dawley (SD) and Long-Evans (LE) rats were ovariectomized (OVX), fitted with indwelling atrial catheters and given a single sc injection of either 25 or 100 micrograms polyestradiol phosphate (PEP); seven days later blood samples were withdrawn at two hour intervals from 1100 to 2100 hours to detect the presence of an afternoon surge of prolactin (PRL). Other groups of OVX rats of both strains also treated with PEP and catheterized as above were sampled before and at 2, 5, 10 and 30 min after iv administration of 1 microgram synthetic thyrotropin releasing hormone (TRH). Pituitary (AP) and uterine weights were determined following sacrifice one day after TRH treatment. Separate groups of OVX rats of both strains treated with 100 micrograms PEP were decapitated 7 days later and each AP was removed and homogenized. The AP homogenates and plasma samples were assayed for PRL by radioimmunoassay. Rats of both strains had afternoon PRL surges and in both strains the magnitude and/or duration of the surges were enhanced by the higher dose of PEP. However, within each PEP dose LE rats released significantly more PRL during the surge than did SD rats. Rats of both strains also released PRL in response to TRH and this response was enhanced in both strains by the higher of the two doses of PEP. However, there were no differences between the strains at 25 micrograms PEP and at 100 micrograms PEP SD rats released significantly more PRL to TRH than did LE rats. Pituitary weight and PRL concentration were not different between the strains at either dose of PEP but LE rats had significantly heavier uteri at both doses of PEP compared to SD rats. These data not only show that strain differences exist in estrogen-induced or mediated PRL release in the rat but also indicate that the differences are not uniform. This latter observation suggests that the estrogen-induced mechanisms examined in this study are for the most part independent of each other.

Animals↗
PubMed1984

The effect of steroids on the size heterogeneity of pituitary prolactin in castrate male rats.

Male Sprague-Dawley rats were castrated and given daily sc. injections of estradiol (E2, 10 micrograms/day), testosterone propionate (TP, 1.0 mg/day), dihydrotestosterone (DHT, 1.0 mg/day) or sesame oil (SO, 0.2 ml/day). A group of sham castrate males received daily sc. injections of SO (0.2 ml/day). On day 8 of steroid treatment animals were decapitated and anterior pituitaries were removed and hemisected. Each half was homogenized in PBS buffer (0.01 M Na2HPO4-NaH2PO4; 0.14 M NaCl; 0.1% bovine serum albumin) at either pH 7.6 or 10.6. Homogenates were chromatographed on Sephadex G-100 columns and eluted fractions were assayed for prolactin (PRL) by RIA. Four immunoreactive forms of PRL, designated as "void volume," "big big," "big" and "little," were eluted from the pituitary homogenates of each experimental group. Homogenates obtained at pH 7.6 contained a greater percentage of PRL in the "void volume" and less activity in the "big" and "little" forms than pH 10.6 homogenates in all experimental groups. Pituitaries from SO- and TP-treated castrate animals contained significantly greater percentages of activity in the "void volume" at pH 7.6 compared to the other groups. At pH 10.6, the pituitary homogenates from the E2-treated group eluted a significantly greater percentage of "big" PRL and a smaller percentage of "little" PRL compared to all other groups. These findings suggest that androgenic and estrogenic steroids may play a role in the pituitary PRL molecular size profile of the male rat.

Animals↗
PubMed1984

Prolactin levels and molecular heterogeneity in rat strains with high and low incidence of DMBA-induced mammary tumors.

We compared the following parameters in Long-Evans (LE) and Sprague-Dawley (SD) female rats: 1) mammary tumor incidence after DMBA, 2) plasma prolactin (PRL) during the estrous cycle before and after DMBA, 3) plasma PRL in immature females from 0900 hr on day 29 to 0900 hr on day 30, 4) plasma PRL from 1200 to 1700 hr and before and 10 min after i.p. TRH administration in ovariectomized (OVX) rats treated with 200 micrograms polyestradiol phosphate (PEP), 5) anterior pituitary (AP) PRL concentration in OVX rats treated with 200 micrograms PEP, and 6) levels and Sephadex G-100 gel filtration patterns of plasma PRL 10 min after i.p. TRH administration in OVX rats treated with 200 micrograms PEP. We observed marked mammary tumor incidence in SD rats from one supplier (S-SD, Spartan) (96%) compared to SD from another supplier (CR-SD, Charles River) (40%) or LE rats (10%). Plasma PRL was significantly decreased on metestrus-diestrus and increased on proestrus-estrus in SD (both suppliers) but not in LE rats 90 days after DMBA compared to rats not given DMBA and sacrificed at same stages of the estrous cycle on day 55 of age. Immature LE and SD-CR females exhibited significant late afternoon and early morning prolactin surges on days 29-30 whereas SD-H rats had either no surges or poorly synchronized surges at the same times.(ABSTRACT TRUNCATED AT 250 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Effect of estrogen administration on the induction of the plasma prolactin afternoon surge and on anterior pituitary prolactin concentration extracted at different pHs.

Ovariectomized (OVX) rats were injected with various doses of polyestradiol phosphate (PEP); the anterior pituitary (AP) prolactin (PRL) concentration and the plasma afternoon surge of PRL were observed 1 week later by radioimmunoassay. AP PRL was extracted using carbonate and phosphate buffers at either pH 7.6 or 10.6. The AP concentration of PRL was greater when the AP was extracted with buffers at pH 10.6 and the phosphate buffer was the most efficient. The concentration of PRL in the AP more closely reflected the magnitude of the estrogen-induced afternoon surge when the AP was extracted at pH 10.6 and this was especially so when the higher levels of estrogen were administered.

Animals↗
PubMed1983

Inhibition of suckling-induced prolactin release by estrogen in ovariectomized lactating rats: bioassay versus radioimmunoassay.

Plasma levels of prolactin (PRL) were determined before and during suckling in intact and ovariectomized (OVX) lactating rats treated 5 days earlier with a single sc injection of 50 micrograms polyestradiol phosphate (PEP) or saline. Radioimmunoassay (RIA) and the Nb2 lymphoma cell bioassay (BA) were used to measure plasma PRL. Pituitary PRL concentrations were also determined by the two assays. In addition, lactational performance was estimated by measuring litter weight gain before and after estrogen treatment. Lactation was inhibited by PEP in intact rats; however, PEP did not alter plasma or pituitary levels of PRL in this group. Lactation was not inhibited by estrogen in OVX rats, but plasma PRL levels were significantly reduced at 10, 30, and 45 min of suckling. In addition, there was no evidence of an estrogen-induced afternoon prolactin surge in either PEP-treated group. The lactational inhibition in the intact, PEP-treated rats was probably due to combined effects of estrogen and progesterone. Plasma progesterone concentration was 64 +/- 8 ng/ml in the intact PEP-treated group compared to 3 +/- 1 ng/ml in the OVX, PEP-treated rats. The exact mechanism for the supression or delay in suckling-induced plasma PRL in the OVX, PEP-treated females remains unresolved but it was not due to an increase in suckling-induced corticosterone levels. The qualitative changes in plasma PRL during suckling in the various groups detected by RIA were also detected by the BA. However, there were slight quantitative differences between the two assays. When plasma PRL was low (nonsuckled states) the BA/RIA ratio was less than that observed when the plasma PRL was high (during suckling), i.e., more bioactive PRL was apparently released by suckling. However, these differences between RIA and BA may have been due in part to the fact that very low or very high levels of prolactin approached the minimal and maximal assay limits of the RIA but not the BA indicating that care be exercised when making such assay comparisons.

Animals↗
PubMed1982

Rat lymphoma cell bioassay for prolactin: observations on its use and comparison with radioimmunoassay.

The rat Nb2 node lymphoma cell bioassay (BA) for prolactin (PRL) was validated for use in our laboratories. During the course of this validation we observed that rat prolactin (NIAMDD-RP-1) stimulated cell division by as much as 16.5 fold over the range of 0.04 to 40.0 ng/ml at the end of 72 hours of incubation. We also observed a dose related increase in the size of the lymphoma cells. Prolactin concentrations in rat plasma, serum, anterior pituitary (AP) homogenates and milk were measured by both radioimmunoassay (RIA) and BA. In individual BA's there was parallelism between samples and standard; but when several dilutions of the same plasma and pituitary homogenates were assayed repeatedly, higher PRL levels were consistently observed for the more concentrated samples. At low or moderate levels of plasma PRL there was excellent agreement between RIA and BA; however, at high levels plasma PRL bioactivity exceeded radioimmunoactivity by a small, but significant, amount. A comparison of pituitary PRL concentrations measured by RIA and BA were in good agreement when homogenization was done at pH 10.6. However, when homogenization was done at pH 7.6, slightly but significantly more PRL was extracted when assayed by BA than when assayed by RIA.

Animals↗
PubMed1979

Evidence for a rapid in vivo effect on estradiol-17 beta on prolactin secretion in ovariectomized rats.

Repeated intraarterial injections of synthetic thryrotropin releasing hormone (TRH, 1 microgram/rat) increased plasma prolactin levels 4 hours after a single subcutaneous injection of 10 micrograms estradiol-17 beta (E2-17 beta) in rats ovariectomized 1, 2 or 4 weeks and at 2 hours after E2-17 beta injection in rats ovariectomized for 6 weeks. The effect of TRH was still present at 24 but not 48 hours after estradiol treatment. TRH-induced increases in plasma prolactin were similar in groups of rats treated with 10 micrograms E2-17 beta (s.c.) or implanted with 0.5 cm Silastic capsules of crystalline E2-17 beta (s.c.) whereas smaller, yet significant, TRH-induced increases in plasma prolactin were observed in rats injected s.c. with 1.0 microgram E2-17 beta. Single intraarterial injections of TRH at 4 or 8 hours after E2-17 beta treatment induced increases in plasma prolactin similar in magnitude to those observed at the same times after E2-17 beta in rats given repeated TRH injections. No effect of TRH was observed in ovariectomized rats given sesame oil and E2-17 beta treatment did not influence plasma prolactin in rats given saline instead of TRH. Intraarterial administration of serotonin creatinine sulfate (5-HT, 10 mg/kg body weight) induced marked increases in plasma prolactin in rats ovariectomized for 4 weeks which were potentiated at 2 and 6 hours after E2-17 beta (10 micrograms) treatment. The data show that estradiol has a fairly rapid stimulatory effect on plasma levels of prolactin induced by two different secretagogues but the exact site and mechanism of action remain unresolved.

Animals↗