Effect of tamoxifen on growth and prolactin secretion of rat pituitary tumours

1983 ◽  
Vol 97 (2) ◽  
pp. 261-266 ◽  
Author(s):  
R. A. Prysor-Jones ◽  
J. J. Silverlight ◽  
J. S. Jenkins

The antioestrogenic drug tamoxifen was administered to rats bearing transplanted prolactin-secreting tumours derived from spontaneously occurring pituitary adenomas in Wistar–Furth rats. Some inhibition of tumour growth was observed but this was accompanied by an increase in plasma prolactin concentrations. Bromocriptine, however, consistently inhibited both growth and prolactin secretion of these tumours. The addition of tamoxifen to bromocriptine treatment produced no increased response to the dopamine agonist. Tamoxifen increased prolactin secretion by tumour cells in vitro but did not affect DNA synthesis. Normal rats responded to tamoxifen with a moderate increase in plasma prolactin concentrations and there was no change in pituitary DNA synthesis.

1977 ◽  
Vol 72 (1) ◽  
pp. 35-39 ◽  
Author(s):  
JOAN JACOBI ◽  
H. M. LLOYD ◽  
J. D. MEARES

SUMMARY The times of onset of oestrogen-induced prolactin secretion and DNA synthesis were studied in the pituitary gland of the male rat. At intervals from 3 to 96 h after injection of 10 mg diethylstilboestrol dipropionate, serum and pituitary prolactin concentrations were measured by radioimmunoassay and pituitary DNA synthesis by incorporation of [3H]thymidine in vitro. Serum prolactin was raised significantly from 6 h onwards and DNA synthesis was increased from 30 h onwards. Pituitary prolactin concentration began to increase at 30 h. Significant correlations were obtained between serum prolactin and DNA synthesis from 24 to 72 h but not during the period of prolactin secretion from 6 to 24 h.


1983 ◽  
Vol 96 (2) ◽  
pp. 347-352 ◽  
Author(s):  
R. A. Prysor-Jones ◽  
J. J. Silverlight ◽  
J. S. Jenkins

Dopamine concentration within the hypothalamus and its depletion after the administration of α-methyl-para-tyrosine were measured in young rats and compared with values obtained in aged animals with and without spontaneously occurring pituitary tumours. Old rats had significantly reduced hypothalamic dopamine concentrations and there was less depletion of dopamine compared with young animals but there were no differences between tumorous and non-tumorous animals. Hyperprolactinaemia induced in young animals caused a much greater depletion of hypothalamic dopamine than in old tumorous rats with comparable plasma prolactin concentrations. The catechol oestrogen 2-hydroxyoestradiol inhibited the release of prolactin from normal rat pituitary glands in vitro but measurement of catechol oestrogens in the hypothalamus showed no differences between young and old tumorous or non-tumorous rats. It is concluded that reduced dopamine concentration and an impaired response to hyperprolactinaemia in old rats may facilitate the growth of prolactin-secreting tumours arising in the pituitary gland.


1981 ◽  
Vol 88 (3) ◽  
pp. 463-469 ◽  
Author(s):  
R. A. PRYSOR-JONES ◽  
J. S. JENKINS

The 'spontaneous' development of pituitary tumours has been studied in the Wistar–Furth strain of rat. In females aged 64–135 weeks the incidence was as high as 69% whereas in males aged 72–116 weeks only 6% developed tumours. Hyperprolactinaemia was invariably associated with these spontaneous pituitary tumours but excessive secretion of growth hormone (GH) was found in one animal only. Bromocriptine inhibited secretion of prolactin and DNA synthesis of the tumours. In a mixed GH- and prolactin-secreting tumour transplanted to a peripheral site, bromocriptine reduced the size of the tumour as well as the secretion of both hormones. Oestradiol reversed the inhibitory action of bromocriptine on prolactin secretion and tumour growth but failed to influence the reduction in GH secretion caused by the drug.


1988 ◽  
Vol 117 (4_Suppl) ◽  
pp. S188-S189
Author(s):  
L. KIESEL ◽  
T. RABE ◽  
D. SCHOLZ ◽  
V. KIRSCHNER ◽  
B. RUNNEBAUM

1980 ◽  
Vol 87 (1) ◽  
pp. 95-103 ◽  
Author(s):  
G. DELITALA ◽  
T. YEO ◽  
ASHLEY GROSSMAN ◽  
N. R. HATHWAY ◽  
G. M. BESSER

The inhibitory effects of dopamine and various ergot alkaloids on prolactin secretion were studied using continuously perfused columns of dispersed rat anterior pituitary cells. Bromocriptine (5 nmol/l) and lisuride hydrogen maleate (5 nmol/l) both inhibited prolactin secretion, the effects persisting for more than 3 h after the end of the administration of the drugs. A similar although less long-lasting effect was observed with lergotrile (50 nmol/l) and the new ergoline derivative, pergolide (5 nmol/l). These effects contrasted with the rapid disappearance of the action of dopamine. The potency estimates of the ergots relative to that of dopamine were: lergotrile, 2·3; bromocriptine, 13; lisuride, 15; pergolide, 23. The dopamine-receptor blocking drugs, metoclopramide and haloperidol, antagonized the prolactin release-inhibiting activity of the compounds; bromocriptine and lisuride showed the highest resistance to this dopaminergic blockade. The results suggested that the direct effect of the ergot derivatives on dispersed pituitary cells was mediated through dopamine receptors and emphasized the long-lasting action of bromocriptine and lisuride in vitro.


1981 ◽  
Vol 90 (3) ◽  
pp. 315-322 ◽  
Author(s):  
ELIZABETH A. LINTON ◽  
NICKI WHITE ◽  
OFELIA LIRA DE TINEO ◽  
S. L. JEFFCOATE

The effects of 2-hydroxyoestradiol (2OH-OE2), dopamine, oestradiol-17β and 2OH-OE2 plus dopamine on prolactin and LH release from the male rat pituitary gland were examined in vitro. 2-Hydroxyoestradiol reduced prolactin secretion by 51% at 10−10 mol/l and by 34% at 10−7 mol/l, while oestradiol-17β had no effect at these doses. Dopamine alone (5 × 10−7 mol/l) decreased prolactin released by 58%, 2OH-OE2 plus dopamine produced a similar inhibition of 60%. No significant effect on LH release was observed throughout.


1969 ◽  
Vol 45 (2) ◽  
pp. 183-NP ◽  
Author(s):  
C. S. NICOLL ◽  
J. A. PARSONS ◽  
R. P. FIORINDO ◽  
C. W. NICHOLS

SUMMARY A procedure for estimating rat prolactin and growth hormone (somatotrophin, STH), by measuring the optical density of the electrophoretically isolated and stained hormone bands in polyacrylamide gel columns, is described and evaluated. A simple and inexpensive densitometer is also described. Prolactin levels in adenohypophyses and in medium from pituitary incubates were measured by electrophoresis-densitometry (ED) and by the pigeon crop-sac assay. The two methods showed a high degree of correlation. The validity of the ED method for estimating prolactin levels in adenohypophysial tissue and in incubation medium was demonstrated by comparing the prolactin content of adult male and female and of oestrogen-treated male glands and by experiments in vitro. The female pituitary contained about three times more prolactin than the male and the glands of oestrogen-treated males had levels about the same as those of females. It was also shown that the ED method could be used to demonstrate the inhibitory effects of extract of rat hypothalamic tissue on prolactin secretion in vitro by the rat pituitary. Levels of STH in adult male glands, as measured by this method, were comparable to results obtained by others using immunoassays. Propylthiouracil-induced hypothyroidism depressed the STH and prolactin levels in male rat pituitaries, in agreement with the observations of others. The stainability of the prolactin band in rat adenohypophyses was observed to decrease with time when the glands were stored on dry ice. No such change occurred in the staining characteristics of the STH band. Other aspects of the ED method are discussed, including its precision, efficiency, sensitivity, economy and utility.


1992 ◽  
Vol 70 (9) ◽  
pp. 2779-2786 ◽  
Author(s):  
J. R. Strickland ◽  
D. L. Cross ◽  
T. C. Jenkins ◽  
R. J. Petroski ◽  
R. G. Powell

1978 ◽  
Vol 87 (4) ◽  
pp. 701-715 ◽  
Author(s):  
F. Peillon ◽  
F. Cesselin ◽  
P. E. Garnier ◽  
A. M. Brandi ◽  
M. Donnadieu ◽  
...  

ABSTRACT To evaluate the in vitro PRL secretion and synthesis by pituitary tumours from acromegalic patients, six somatotrophic and two somatomammotrophic adenomas were collected after surgery and divided into fragments 1 mm3 in size. Fragments were cultured in short-term (1–2–3–4 h) and in long-term organ culture (7 and 14 days). Media were collected for GH and PRL radioimmunoassay and fragments studied by electron microscopy. In two experiments, fragments from a somatotrophic adenoma and from a somatomammotrophic adenoma were cultured for 1 to 4 h and 9 to 16 days with [3H]leucine. In addition the effect of somatostatin (2.5 nmole/ml) upon PRL secretion was studied in short-term incubation. In long-term organ culture PRL concentrations increased in 8 out of 16 media samples collected from the five tumours and one normal pituitary cultured for 14 days, while GH concentrations decreased during the same time in all the experiments. The [3H]PRL/[3H] proteins ratios were 9.7 % on the 9th day of culture and 20.8 % on the 16th day while for GH, the ratios were respectively 40 and 34.7 %. Ultrastructural studies showed, besides GH cells, the presence of PRL secreting cells in the different tumours, after 7 or 14 days of culture. In short-term incubation, PRL concentrations in media increased in most of the samples collected from the three tumours incubated for 1 to 4 h and the [3H]PRL/[3H]proteins ratio was 10.6 % after 1 h and 21 % after 2 h of incubation. A decrease of PRL content (< 50 %) was observed in two of the three tumours incubated with somatostatin. These data indicate that 1) somatotrophic adenomas, as well as somatomammotrophic ones, are able to secrete and synthesize PRL in vitro, 2) PRL synthesis from these adenomas increases during culture, as from normal pituitary, presumably because of the release of PRL-secreting cells from the PRL inhibitory hypothalamic control (PIF), 3) somatostatin may reduce PRL release in vitro from somatotrophic adenomas as reported in some cases in vivo.


1987 ◽  
Vol 115 (2) ◽  
pp. 196-202 ◽  
Author(s):  
Steven W. J. Lamberts ◽  
Theo Verleun ◽  
Joke M. Zuiderwijk ◽  
Rob Oosterom

Abstract. The somatostatin analog SMS 201-995 was recently shown to be effective in suppressing GH secretion and in causing tumour shrinkage in patients with GH-secreting pituitary tumours. In this respect, the action of SMS 201-995 seems similar to that of the dopamine-agonist bromocriptine in patients with PRL-secreting pituitary tumours. In the present study we compared the respective effects of SMS 201-995 and bromocriptine on normal rat GH and PRL release in vivo and in vitro. Both in vitro and in vivo, repeated administration of SMS for up till 6 days suppressed circulating GH concentrations, and the ability of the pituitary glands to release GH in vitro. A dose-dependent diminution occurred of the total pituitary GH content in rats treated in vivo with SMS 201-995 for 4–6 days. During short-term in vitro incubation for only 4 h, the total amount of GH measured in the medium + gland was also diminished. Chronic administration with SMS 201-995 (2 μg/kg twice daily for 15 days), however, resulted in a complete desensitization of its inhibitory effect on GH synthesis and release. In similar experiments it was shown that the dopamine agonist bromocriptine affects normal PRL secretion in a different manner. Both in vitro (10 nmol/l) and in vivo administration for 6 days (0.2 mg/kg twice daily) greatly inhibited circulating PRL levels and the ability of the pituitary glands to release PRL in vitro. This is, however, in all instances accompanied by an accumulation of PRL within the pituitary gland. Long-term bromocriptine administration (0.2 mg/kg twice daily for 15 days) inhibited PRL secretion, and finally also a decrease in the total pituitary PRL content was observed. It is shown in this study that SMS 201-995 and bromocriptine affect hormone release by normal pituitary glands in a different manner. SMS 201-995 acutely inhibits GH release and diminishes within a few hours of exposure also the GH content in normal cells by a powerful inhibition of GH synthesis and/or an increase in intracellular degradation of GH. Bromocriptine, however, exerts primarily an inhibitory effect on PRL release, whereas an inhibition of synthesis and/or degradation of intracellular PRL is evident only after long-term exposure to the drug.


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