High tumour prolactin receptor content and lack of increase in serum prolactin levels as predictors of good response to endocrine therapy in rat mammary cancer

1988 ◽  
Vol 41 (5) ◽  
pp. 767-770 ◽  
Author(s):  
F. di Carlo ◽  
G. Muccioli ◽  
G. Bellussi ◽  
G. Conti ◽  
S. Racca
1984 ◽  
Vol 103 (3) ◽  
pp. 287-293 ◽  
Author(s):  
F. Di Carlo ◽  
S. Racca ◽  
G. Conti ◽  
E. Gallo ◽  
G. Muccioli ◽  
...  

ABSTRACT The changes in oestrogen, progesterone and prolactin receptor levels in target organs, and the macroscopic and microscopic modifications of uterus, ovary, adrenal and pituitary gland induced by long-term administration of high doses of medroxyprogesterone acetate (MPA) were investigated in female rats. Medroxyprogesterone acetate was injected i.m. for 30 days at daily doses of 7·5, 15 and 75 mg/kg. Oestrogen and/or progesterone-binding capacities were remarkably reduced at all doses of MPA used both in the uterus and pituitary gland. Furthermore, MPA caused a very evident reduction in the weight of pituitary glands, ovaries, adrenals and uterus. In all MPA-treated rats corpora lutea were absent from the ovaries, whereas the adrenals showed a significant reduction in the thickness of the cortex. In accordance with this, there was no evidence of ACTH-producing cells in the pituitary glands. Prolactin-producing cells were also absent, while GH-producing cells were present. Serum prolactin levels were significantly reduced at all doses of MPA used. A dramatic reduction of prolactin receptor concentrations was observed in the liver and the ovaries of MPA-treated rats. The results suggest that MPA acts as an antioestrogenic drug both by reducing the number of oestrogen receptors in target tissues and by changing the structure (and perhaps the function) of those organs (pituitary glands, ovaries and adrenals) which are, directly or indirectly, a source of oestrogens. The decreased synthesis of prolactin and the reduction of the number of prolactin receptors (which, on the contrary, are both increased by oestrogens) might be considered as additional antioestrogenic effects of MPA. J. Endocr. (1984) 103, 287–293


2019 ◽  
Vol 38 (4) ◽  
pp. 318-325 ◽  
Author(s):  
Chimeddulam Erdenebaatar ◽  
Munekage Yamaguchi ◽  
Mahina Monsur ◽  
Fumitaka Saito ◽  
Ritsuo Honda ◽  
...  

1975 ◽  
Vol 149 (1) ◽  
pp. 133-135 ◽  
Author(s):  
P.-C. Chan ◽  
F. Didato ◽  
L. A. Cohen

1994 ◽  
Vol 142 (3) ◽  
pp. 535-545 ◽  
Author(s):  
R W Carón ◽  
G A Jahn ◽  
R P Deis

Abstract We studied the capacity of different GH preparations, natural human (h)GH, recombinant hGH (rhGH), rat (r)GH, ovine (o)GH, bovine (b)GH and porcine (p)GH, and ovine prolactin (oPRL), to stimulate lactogenesis in ovario-hysterectomized pregnant rats or intact lactating rats treated with bromocriptine (BC). Ovariohysterectomy (OVX-HYS) performed at 0800 h on day 19 of pregnancy induced lactogenesis, i.e. increases in mammary casein and lactose and positive response to the oxytocin test, 28 h later. Lactogenesis was prevented by treatment with BC (1·5 mg/kg) immediately after surgery (OVX-HYS-BC). The hormones were given at doses of 0·25 or 0·5 mg/rat (except rhGH given only at 0·5 mg/rat) at 1200 and 2000 h on day 19. Casein was increased by both doses of oPRL and hGH, rhGH and 0·25 mg oGH, and lactose by both doses of oPRL, rhGH and 0·25 mg rGH. The other GH preparations had no effect. The oxytocin test demonstrated the presence of milk in the mammary tissues of the OVX-HYS rats and in the OVX-HYS-BC plus oPRL (0·25 and 0·5 mg) or rhGH-treated groups. Injection of BC to pregnant rats at 2000 h on day 20 and at 0800 h on day 21 decreased litter growth on the first 4 days postpartum. Two-thirds of the litters resumed growth after day 4, indicating the recuperation of milk production, while the rest never recuperated. Serum prolactin in BC-treated rats was reduced until day 4 postpartum. On day 6 the rats which had recuperated had normal values, while those which had still not recuperated had lower values. BC-treated rats were injected s.c. with 0·25 mg each of oPRL, hGH, rGH, oGH, bGH or pGH, or 0·25 or 0·5 mg rhGH/rat, immediately postpartum and 12, 24 and 36 h later. hGH and 0·5 mg rhGH induced levels of milk production similar to controls except on day 3. oPRL and rhGH (0·25 mg), induced a partial reversion of the effect of BC. rGH and oGH had a slight effect on days 1 and 2 and all the litters resumed growth on day 7. In contrast, pGH and bGH were inactive. The affinity of hGH for the prolactin receptor, measured as displacement of 125I-labelled oPRL binding to crude liver membranes, was comparable with that of oPRL. While rhGH was ten times less active than oPRL, rPRL was 100 times lower and all the other GH preparations had at least 104 times lower capacity to displace 125I-labelled oPRL. These results indicate that both natural and recombinant hGHs are potent inductors of milk synthesis in pregnant or lactating rats, most probably due to their actions at the level of the prolactin receptor. rGH and oGH have a partial action, while pGH and bGH seem to be inactive. The actions of non-human GHs may be explained by their somatogenic properties exclusively, and indicate that GH may play a role in the optimization of milk production during lactation and an accessory role in the induction of lactogenesis in pregnant rats. Journal of Endocrinology (1994) 142, 535–545


1978 ◽  
Vol 102 (6) ◽  
pp. 127-128 ◽  
Author(s):  
J. Hamilton ◽  
P. Knight ◽  
J. Beevers ◽  
R. Else

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Munekage Yamaguchi ◽  
Chimeddulam Erdenebaatar ◽  
Fumitaka Saito ◽  
Ritsuo Honda ◽  
Takashi Ohba ◽  
...  

Abstract To elucidate the mechanism of endometrial cancer (EC) development in young hyperprolactinemic women, this study assessed the hormonal receptor expression, proliferation, and signaling induced by prolactin in endometrial glands (EG) and EC. Prolactin receptor (PRLR) and estrogen receptor alpha (ER-α) in EG were evaluated during the menstrual cycle by immunohistochemistry. The following parameters were compared between EM-E6/E7/TERT cells, which originated from proliferative EG and Ishikawa cells. The expression levels of PRLR, pJAK2 (phosphorylated Janus Activating Kinase 2), its downstream pathways (MAPK, PI3K, and STAT), and ER-α were assessed after adding prolactin by Western blotting. U0126 was used as a MAPK inhibitor. The proliferation caused by estradiol was also examined by MTS assay after adding prolactin. PRLR expression in the EG was significantly higher in the proliferative phase than in the secretory phase, and it was correlated with ER-α expression during the menstrual cycle. After adding prolactin, the expression of pJAK2, PRLR and ER-α was significantly increased in both cell lines, MAPK was activated after adding prolactin in both cell lines, and PI3K and STAT were activated only in EM-E6/E7/TERT cells. The increased proliferation induced by estradiol was enhanced after adding prolactin in both cell lines. All changes caused by prolactin were inhibited in Ishikawa cells pretreated with U0126. Long-term effects of serum prolactin on persistent proliferative endometrium in the presence of estradiol may induce abnormal proliferation of EG in hyperprolactinemic women. Prolactin-PRLR signaling via MAPK may play a crucial role in the progression of EC in hyperprolactinemic women.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12568-e12568
Author(s):  
Ricardo Lima Barros Costa ◽  
Cesar Augusto Santa-Maria ◽  
Denise M. Scholtens ◽  
Sarika Jain ◽  
William John Gradishar ◽  
...  

e12568 Background: The prolactin receptor can be overexpressed in breast cancer, and pre-clinical data indicate that it contributes to the pathobiology of breast cancer. Cabergoline is a potent dopamine receptor agonist of D2 receptors and has a direct inhibitory effect on pituitary prolactin secretion resulting in reduced serum prolactin levels. Methods: A pilot phase II study of cabergoline in patients with metastatic breast cancer was conducted with primary end point of best overall response rate (ORR) among patients with measurable disease. Eligible patients had metastatic breast cancer, any receptors status was allowed, and there was no limit of prior lines of therapy. Both measurable and unmeasurable diseases (RECIST 1.1) were allowed. Cabergoline 1mg orally, twice weekly (1 cycle = 4 weeks) was given until disease progression or unacceptable toxicity. Immunohistochemistry prolactin receptor staining was performed on available baseline tumor tissue, and serum prolactin levels were serially assessed. Results: A total of 20 women were enrolled, 19 of whom were evaluable for response (one patient died on C1D7 of unrelated causes). Mean age was 62 (range 42-83); 15 (75%) were Caucasian; mean number of prior lines of therapy 5 (range 0-14). Tumor receptor statuses were distributed as follows: HR+/HER2+ 1(5%), HR+/HER2- 18 (80%), HR-/HER2+ 1 (5%). Analysis was performed after a median follow-up of 6.8 months (0.2-26.2). Best ORR was 8.3% among 12 patients with measurable disease. Results for secondary endpoints were as follows: 4-month CBR = 26% (including patients with measurable and non-measurable disease), median PFS = 1.9 months, and median OS = 10.4 months. Most common treatment related AEs were nausea (30%), fatigue (25%), and elevation in alkaline phosphatase (15%). The highest-grade AE was a single grade 3 treatment-related pain in extremity. Nine patients had sufficient baseline tissue for analysis, there was no correlation between baseline tumor prolactin receptor expression and clinical benefit ( p= 0.24). Additional correlative work is ongoing. Conclusions: Cabergoline was well tolerated and associated with modest anti-tumor activity. Clinical trial information: NCT01730729.


2001 ◽  
Vol 29 (2) ◽  
pp. 48-52 ◽  
Author(s):  
P. A. Kelly ◽  
N. Binart ◽  
M. Freemark ◽  
B. Lucas ◽  
V. Goffin ◽  
...  

Prolactin-receptor-deficient mice are a good model in which to study the various actions of prolactin. Female homozygous knockout mice are completely infertile and show a lack of mammary development, while hemizogotes are unable to lactate following their first pregnancy. Male and female homozygotes have markedly elevated serum prolactin levels, and in some instances pituitary hyperplasia is present. Maternal behaviour is severely affected in both hemizygous and homozygous animals. Bone formation is reduced in young animals and in adults (males and females). Finally, older males and females show a slight reduction in body weight, which seems to be due to reduced abdominal fat deposition in the knockout animals.


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