scholarly journals Effects of Parity and Serum Prolactin Levels on the Incidence and Regression of DMBA-Induced Tumors in OFA hr/hr Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Corina V. Sasso ◽  
Flavia E. Santiano ◽  
Constanza M. López-Fontana ◽  
Virginia Pistone-Creydt ◽  
Marcelo E. Ezquer ◽  
...  

Prolactin (PRL) is a key player in the development of mammary cancer. We studied the effects of parity or hyperprolactinemia on mammary carcinogenesis in OFA hr/hr treated with 7,12-dimethylbenzanthracene. They were divided into three groups: nulliparous (Null), primiparous (PL, after pregnancy and lactation), and hyperprolactinemic rats (I, implanted in the arcuate nucleus with 17β-estradiol). The tumor incidence was similar in the three groups. However, a higher percentage of regressing tumors was evident in the PL group. Serum PRL, mammary development, and mammaryβ-casein content were higher in I rats compared to Null. The expression of hormone receptors was similar in the different groups. However, mammary tissue from PL rats bearing tumors had increased expression of PRL and estrogen alpha receptors compared to rats free of tumors. Our results suggest that serum PRL levels do not have relevance on the incidence of tumors, probably because the low levels of PRL in OFA rats are not further decreased by PL like in other strains. However, supraphysiological levels of PRL affect carcinogenesis. PL induces regression of the tumors due to the differentiation produced on the mammary cells. Alterations in the expression of hormonal receptors may be involved in progression and regression of tumors.

1994 ◽  
Vol 301 (3) ◽  
pp. 807-812 ◽  
Author(s):  
R A Gardner ◽  
M T Travers ◽  
M C Barber ◽  
W R Miller ◽  
R A Clegg

‘Expressed’ and ‘total’ activities of cyclic AMP-dependent protein kinase (PK-A) were measured in extracts of rat mammary tissue sampled throughout pregnancy and lactation. Expression of the genes encoding the catalytic subunit (C-subunit) isoforms C alpha and C beta was examined by Northern blotting, as a function of mammary development, to determine relative levels of their respective mRNAs. The content of C-subunit protein (all isoforms) was estimated immunochemically and related to levels of C-subunit catalytic activity and of mRNAs. It was found that C-subunit isoform mRNAs are expressed co-ordinately during mammary development and that a marked decline in expression, per cell, at around parturition is paralleled by a fall in ‘total’ PK-A activity. The ‘expressed’ activity of PK-A activity underwent characteristic changes throughout pregnancy and lactation, reaching a peak late in pregnancy. The PK-A activity ratio reached a peak in early lactation. C-subunit protein mass closely parallel ‘total’ PK-A activity throughout pregnancy and lactation, thereby demonstrating the constancy of C-subunit specific catalytic activity during these developmental events. Regulatory subunits (R-subunits) were probed with the photoaffinity label 8-azido-[32P]cAMP. The abundance of R-II as a proportion of total R-subunit increased throughout pregnancy and lactation, and quantitative analysis of the photoaffinity labelling suggested inconstancy in the ratio of R:C subunits, with highest values occurring in late pregnancy/early lactation.


2005 ◽  
Vol 72 (S1) ◽  
pp. 51-57 ◽  
Author(s):  
John P Wiebe

Among the species investigated, the rate of spontaneous cancers of mammary glands is highest in humans and dogs (Hamilton, 1974; Owen, 1979). In addition, spontaneous mammary tumours are known to occur in strains of mice (Webster & Muller, 1994), rats (Russo et al. 1990; Sukumar, 1995) and cats (Hamilton, 1974; Kessler & von Bombard, 1997). Although both oestrogen and progesterone are known to be involved in normal mammary development as well as in the proliferative changes that occur during the oestrous or menstrual cycle, pregnancy and lactation (Going et al. 1988), only the role of oestradiol has been extensively investigated. The role of progesterone in mammary cancer is not understood and, although progesterone metabolism is known to occur in mammary tissue, the potential autocrine/paracrine role of the in situ metabolites has only recently begun to be explored in human breast tissues and cell lines (Wiebe et al. 2000).


2003 ◽  
Vol 83 (4) ◽  
pp. 731-737 ◽  
Author(s):  
C. Farmer ◽  
M. F. Palin ◽  
M. T. Sorensen

Endocrine and metabolic data as well as mammary tissue composition were obtained in Genex-Meishan (GM, containing 50% Chinese Meishan genes) and Large White (LW) lactating sows. Jugular vein cannulae were used to collect serial blood samples from 9 LW and 8 GM sows for 4 h every 15 min on days 6 and 19 of lactation. Concentrations of prolactin and cortisol were determined on all samples while those of insulin-like growth factor-I (IGFI), growth hormone (GH), glucose and free fatty acids (FFA) were measured in hourly samples. Milk samples were obtained from 19 GM and 16 LWsows on day 23 of lactation and all sows were slaughtered on day 25. Mammary glands were excised and analyzed for tissue composition and for number and affinity of prolactin receptors. Concentrations of plasma IGF-I were lower (P < 0.01) and plasma FFA greater (P < 0.001) in GM than in LW sows. On day 6 of lactation, serum prolactin (P < 0.05) and cortisol (P < 0.01) concentrations were greater and glucose values lower (P < 0.001) in GM than in LW sows. The concentration of IGFI in lactoserum was lower (P < 0.001) while that of prolactin was greater (P < 0.05) in GM compared to LW sows on day 23 of lactation. There was less (P < 0.001) residual milk and more (P < 0.05) parenchymal RNA in mammary glands from GM compared to LW sows. The affinity of prolactin receptors was also greater (P < 0.05) in GM than in LW sows. The better emptying of mammary glands by litters from GM sows and the greater circulating concentrations of prolactin in early lactation as well as the greater affinity of mammary prolactin receptors may be related to the great milking potential of Meishan-derived sows. Key words: Hormones, lactation, mammary gland, Meishan, prolactin, sows


1980 ◽  
Vol 86 (3) ◽  
pp. 730-737 ◽  
Author(s):  
S Z Haslam ◽  
G Shyamala

The biological basis for the observed modulation in cytoplasmic progesterone receptors (PgR) of normal mammary gland occurring during mammary development was investigated. Specifically, the relative roles of hormones vs. differentiation on (a) the decrease in PgR concentration during pregnancy and lactation and (b) the loss of mammary responsiveness to estrogen during lactation were examined. PgR were measured using the synthetic progestin, R5020, as the ligand. The hormones estrogen and progesterone were tested in vivo for their effect of PgR concentration. Mammary gland differentiation was assessed morphologically and by measuring enzymatically active alpha-lactalbumin. These studies show that there is a stepwise decrease in PgR that occurs in two stages. The first decrease is completed by day 12 of pregnancy and the second decrease occurs only after parturition. There appears to be a hormonal basis for the first decrease and it appears to be caused by the negative effect of progesterone on estrogen-mediated increase in PgR. In direct contrast, the absence of PgR during lactation and the mammary tissue insensitivity to estrogenic stimulation of PgR were not related to the hormonal milieu of lactation but were directly related to the secretory state of the mammary gland and lactation per se.


1991 ◽  
Vol 58 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Paul A. Fowler ◽  
Christopher H. Knight ◽  
Margaret A. Foster

SummaryMammogenesis and lactation were induced in five multiparous, non-pregnant goats by treatment with oestrogen and progesterone for 11 d, followed by dexamethasone for 3 d. Reserpine was administered during the last 5 d. All five goats lactated, although milk yield was less than had been achieved in previous natural lactations. Mammary development was assessed in vivo, using magnetic resonance imaging. Although parenchyma volume increased by more than 6-fold overall, only 25% of this increase occurred during steroid treatment. Most development took place after the cessation of treatment, when milking commenced. Maximum size was not achieved until week 8 of the induced lactation, and was only 70% of normal parenchyma volume. After 18 weeks lactation the activities of three key milk synthetic enzymes were very similar to values previously found in natural lactations, and secretion efficiency (milk production per unit volume of parenchyma) was also similar to that of natural lactations. We conclude that the lower than normal milk yields were associated with incomplete proliferation of mammary tissue, rather than inadequate differentiation of individual secretory cells.


Author(s):  
Julian R. E. Davis

Prolactin is a polypeptide hormone, named from its well-known effects to promote lactation. It is essential for successful reproduction in man and mammals, although it is known to have a wide variety of nonreproductive effects whose clinical significance remains uncertain. Hyperprolactinaemia, reflecting sustained overproduction of lactin by the pituitary, is relatively common in the population. The commonest cause is the use of drugs that have dopamine D2 receptor antagonist activity (e.g. antipsychotic agents such as phenothiazines), pregnancy and lactation are the commonest physiological causes, and short-term acute stress, such as the anxiety provoked by blood sampling, is also a frequent cause of transient rises in serum prolactin that may be misinterpreted and necessitate a second confirmatory blood sample. Pathological pituitary causes of hyperprolactinaemia may reflect a functioning pituitary prolactinoma, but in many cases no adenoma is detectable on scanning, in which case the condition is termed idiopathic or nontumoral hyperprolactinaemia. The typical clinical features that suggest hyperprolactinaemia are those of galactorrhoea and oligo-/amenorrhoea. Weight gain has been reported in hyperprolactinaemic women, as has insulin resistance. Serum prolactin levels are readily measured by most clinical biochemistry laboratories, and prolactin levels should be measured on more than one occasion, with persistent unexplained hyperprolactinaemia requiring evaluation. Patients with hyperprolactinaemia may require treatment for various reasons, including restoration of ovulatory function, maintenance of adequate oestrogenization, suppression of galactorrhoea, or reduction in size of a mass lesion. Depending on the presentation and underlying cause, there are several treatment options; the main current treatment option is dopamine agonist therapy, surgery and (rarely) radiotherapy are also used in the treatment of prolactinomas.


2013 ◽  
Vol 305 (6) ◽  
pp. C623-C631 ◽  
Author(s):  
Takuya Matsumoto ◽  
Eiji Nakamura ◽  
Hidehiro Nakamura ◽  
Mariko Hirota ◽  
Ana San Gabriel ◽  
...  

The concentration of free glutamate (Glu) in rat's milk is ∼10 times higher than that in plasma. Previous work has shown that mammary tissue actively transports circulatory leucine (Leu), which is transaminated to synthesize other amino acids such as Glu and aspartate (Asp). To investigate the molecular basis of Leu transport and its conversion into Glu in the mammary gland, we characterized the expression of Leu transporters and [3H]Leu uptake in rat mammary cells. Gene expression analysis indicated that mammary cells express two Leu transporters, LAT1 and LAT2, with LAT1 being more abundant than LAT2. This transport system is sodium independent and transports large neutral amino acids. The Leu transport system in isolated rat mammary cells could be specifically blocked by the LAT1 inhibitors 2-aminobicyclo-[2.2.1]-heptane-2-carboxylic acid (BCH) and triiodothyronine (T3). In organ cultures, Glu secretion was markedly inhibited by these LAT1 inhibitors. Furthermore, the profiles of Leu uptake inhibition by amino acids in mammary cells were similar to those reported for LAT1. In vivo, concentrations of free Glu and Asp increased in milk by oral gavage with Leu at 6, 12, and 18 days of lactation. These results indicate that the main Leu transporter in mammary tissue is LAT1 and the transport of Leu is a limiting factor for the synthesis and release of Glu and Asp into milk. Our studies provide the bases for the molecular mechanism of Leu transport in mammary tissue by LAT1 and its active role on free Glu secretion in milk, which confer umami taste in suckling pups.


2013 ◽  
Vol 93 (1) ◽  
pp. 1-7 ◽  
Author(s):  
C. Farmer

Farmer, C. 2013. Review: Mammary development in swine: effects of hormonal status, nutrition and management. Can. J. Anim. Sci. 93: 1–7. There are three phases of rapid mammary accretion in swine, namely, from 90 d of age until puberty, during the last third of gestation and throughout lactation. Nutrition, endocrine status and management of gilts or sows during those periods can affect mammary development. More specifically, in growing gilts, feed restriction as of 90 d of age hinders mammary development and either supplying the phytoestrogen genistein or increasing circulating concentrations of prolactin stimulates mammogenesis. In late gestation, inhibition of relaxin or prolactin drastically diminishes mammary development and overly increasing dietary energy has a detrimental effect on mammogenesis. It also appears that feeding of the gestating sow can affect the mammary development of her offspring once it reaches puberty. Various management factors such as litter size, nursing intensity and use or non-use of a teat in the previous lactation will affect the amount of mammary tissue present at the end of lactation. Mammary development is followed by the essential process of involution whereby a rapid and drastic regression in parenchymal tissue takes place. It can occur either after weaning or in early lactation when teats are not being regularly suckled. Despite our current knowledge, much remains to be learned in order to develop the best management strategies for replacement gilts, and gestating and lactating sows that will maximize their milk production.


2008 ◽  
Vol 20 (4) ◽  
pp. 460 ◽  
Author(s):  
Rachael O'Dowd ◽  
Mary E. Wlodek ◽  
Kevin R. Nicholas

Adequate mammary development and coordinated actions of lactogenic hormones are essential for the initiation of lactation. Pregnancies compromised by uteroplacental insufficiency impair mammary development and lactation, further slowing postnatal growth. It is not known whether the initiation of lactation or galactopoesis is compromised. Uteroplacental insufficiency induced in rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on Day 18 of gestation preceded collection of mammary tissue on Day 20 of pregnancy. Mammary explants were cultured with combinations of insulin, cortisol and prolactin and analysed for α-lactalbumin and β-casein gene expression. Mammary tissue from late pregnant Restricted rats had elevated α-lactalbumin, but not β-casein, mRNA, which is consistent with premature lactogenesis resulting from an early decline in peripheral maternal progesterone. Explants from Restricted rats were more responsive to hormone stimulation after 3 days in culture, indicating that compromised galactopoesis, not lactogenesis, most likely leads to the reduced growth of suckled pups.


1986 ◽  
Vol 111 (4) ◽  
pp. 567-571
Author(s):  
Stacey R. Swartz ◽  
Linda Ogren ◽  
Frank Talamantes

Abstract. Pituitary responsiveness to dopamine was investigated on several days of pregnancy in the mouse. Sera and anterior pituitary glands were obtained at 09.00 and 18.00 h on day 5 of pregnancy and at 09.00 h on days 12 and 18, and the pituitaries were incubated for 5 h in several concentrations of dopamine (0, 5 × 10−10—5 × 10−7 m). Serum prolactin (Prl) concentration was the highest on day 5 (18.00 h sample), followed by day 18 (09.00 h), day 5 (09.00 h) and day 12 (09.00 h). Pituitary responsiveness to dopamine was assessed on each day of pregnancy by determining the slopes of dose-response curves in which the Prl concentration of the medium was plotted as a function of dopamine concentration. The slope of the dose-response curve for pituitaries from day 12 or pregnancy was significantly steeper than the slopes of the curves for pituitaries from days 5 and 18, which did not differ from each other. These data suggest that the Prl secretion mechanism is more sensitive to inhibition by dopamine on day 12 of pregnancy, when serum Prl concentration is very low, than on days 5 or 18, when serum Prl concentrations are higher. One of the mechanisms by which circulating Prl concentrations are reduced to very low levels during midpregnancy in the mouse may be increased pituitary sensitivity to dopamine.


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