THE EFFECT OF CORTISOL ACETATE ON OESTRONE-INDUCED MAMMARY GLAND GROWTH IN IMMATURE OVARIECTOMIZED ALBINO MICE

1957 ◽  
Vol 16 (1) ◽  
pp. 72-79 ◽  
Author(s):  
R. E. MUNFORD

SUMMARY The response of the mammary glands of ovariectomized albino mice to treatment with 0·003 or 0·006 μg oestrone daily could be distinguished after 21 days of treatment. Differences in mammary gland areas of oestrone-treated ovariectomized mice, and of both ovariectomized and intact controls, were significant. When injected at a level of 12·5 μg daily for 21 days, cortisol acetate (CA) stimulated mammary development in ovariectomized and ovariectomized oestrone-treated albino mice, both growth in area and increase in the number of duct junctions being affected. At higher dosage rates (25 and 50 μg daily) CA was without detectable influence on the mammary glands. The effect of the two steroids upon the mammary glands appeared to be simply additive when analysed on the transformed (logarithmic) scale. The estimate of the density of duct branching—number of duct junctions per unit area—of the mammary glands was not significantly affected by either steroid. Differences in this estimate of mammary gland structure were in general inversely related to differences in area or number of duct junctions. The effects of treatment with CA and with oestrone upon the body weight, adrenal and thymus gland weight, uterine weight and vaginal changes were also observed.

1957 ◽  
Vol 15 (3) ◽  
pp. 266-272 ◽  
Author(s):  
D. S. FLUX

SUMMARY Ovariectomized mice, treated with a preparation of growth hormone (GH) containing thyrotrophic hormone (TSH), showed increased mammary duct growth and increased uterine weight. The effect of the amount of GH used was similar in mice treated either with or without oestrone. Similar mice, treated with l-thyroxine, showed increased uterine weight but no significant effect on mammary duct growth. It appears that TSH may have been responsible for the effect of GH on uterine weight but not for its effect on mammary duct growth.


2009 ◽  
Vol 68 (4) ◽  
pp. 340-349 ◽  
Author(s):  
Saverio Cinti

All mammals are provided with two distinct adipose cells, white and brown adipocytes. White adipocytes store lipids to provide fuel to the organism, allowing intervals between meals. Brown adipocytes use lipids to produce heat. Previous descriptions have implied their localization in distinct sites of the body; however, it has been demonstrated that they are present together in many depots, which has led to the new concept of the adipose organ. In order to explain their coexistence the hypothesis of reversible physiological transdifferentiation has been developed, i.e. they are contained together because they are able to convert, one into the other. In effect, if needed the brown component of the organ could increase at the expense of the white component and vice versa. This plasticity is important because the brown phenotype of the organ is associated with resistance to obesity and its related disorders. A new example of reversible physiological transdifferentiation of adipocytes is offered by the mammary gland during pregnancy, lactation and post-lactation stages. The gravidic hormonal stimulus seems to trigger a transdifferentiation of adipocytes into milk-producing and secreting epithelial glands. In the post-lactation period some of the epithelial cells of the mammary gland seem to transdifferentiate into adipocytes. Recent unpublished results suggest that explanted adipose tissue, as well as explanted isolated mature adipocytes, is able to transdifferentiate into glands with epithelial markers of milk-secreting mammary glands. These findings, if confirmed, seem to suggest new windows into the cell biology frontiers of adipocytes.


1983 ◽  
Vol 50 (4) ◽  
pp. 405-412 ◽  
Author(s):  
Roger D. Harrison ◽  
Ian P. Reynolds ◽  
William Little

SUMMARYThe mammary glands of conventionally reared cows, never exceeding a live weight gain (LWG) of 0·74 kg/d, weighed 39% more and contained 68% more secretory tissue than glands of rapidly reared animals grown at 1·1 kg/d. In 11-month-old heifers reared at 3 rates of LWG (L, 0·57; M, 0·76 and H, 1·18 kg/d) gland weight was related to LWG, but dissected mammary parenchyma was heavier in animals on treatment L than on treatment H and followed a quadratic relationship. Parenchymal composition on treatment H was correlated to both age and body weight at puberty. No similar trend was observed in treatments L and M although group L animals had more ductal tissue and less fat than those of group M. Heifers from treatment L were reared during pregnancy at either 0·68 or 0·84 kg/d LWG (treatments LL and LH respectively) and heifers from treatment H at 0·58 kg/d (treatment HL). Total gland weight was unaffected by treatment, but the percentage by weight of secretory tissue in the gland in treatment HL was less than for treatments LL and LH. These experiments confirm that mammary development is permanently impaired by high rates of LWG in the first year of life. There was no impairment of mammary development in heifers reared moderately in the first year and more rapidly during pregnancy.


1962 ◽  
Vol 41 (2) ◽  
pp. 287-300 ◽  
Author(s):  
Dora Jacobsohn

ABSTRACT In a previous study it was found that oestrogens are necessary for androgens to elicit a development of alveolar lobules in the mammary glands of rats. Since androgens and oestrogens exert synergistic as well as antagonistic actions on mammary glands of e. g. rabbits, the significance of oestrogens in the response of the mammary gland to androgens was further investigated in the rat. The experiments were designed according to the same principles as previously, that is, the response of the gland itself to oestrogens was modified. This was achieved by treatment of hypophysectomized rats with a) thyroxine (negligible response) and b) thyroxine, cortisone and insulin (marked response). The effect of endogenous androgens was studied in males injected with PMS with or without oestrogens. Gonadectomized rats were injected with testosterone and oestrogens. No oestrogens given: The mammary glands of hypophysectomized males injected with PMS showed an abnormal response, irrespective of simultaneous treatment with thyroxine, cortisone and insulin in various combinations. The result confirms previous work with testosterone. Negligible response of the mammary glands to oestrogens: In hypophysectomized rats treated with thyroxine, oestrogens and PMS or testosterone, the response of the glands was uniform and abnormal. The absence of end buds indicated that the response to oestrogens, if present at all, was suppressed by the androgens. Marked response of the mammary glands to oestrogens: In hypophysectomized rats treated with thyroxine, cortisone and insulin another response of the glands to androgens and oestrogens was found. Besides abnormal structures, alveolar lobules were present. The changes produced with different doses of testosterone and oestrone indicated a complicated interplay of the two hormones. Confirming previous observations, records of the length and weight of the body and of the weight of the liver and heart revealed marked growth in the hypophysectomized rats treated with thyroxine, cortisone and insulin.


2016 ◽  
Vol 371 (1710) ◽  
pp. 20150416 ◽  
Author(s):  
Jacqulyne P. Robichaux ◽  
John W. Fuseler ◽  
Shrusti S. Patel ◽  
Steven W. Kubalak ◽  
Adam Hartstone-Rose ◽  
...  

Left–right (L–R) differences in mammographic parenchymal patterns are an early predictor of breast cancer risk; however, the basis for this asymmetry is unknown. Here, we use retinoid X receptor alpha heterozygous null (RXRα +/− ) mice to propose a developmental origin: perturbation of coordinated anterior–posterior (A–P) and L–R axial body patterning. We hypothesized that by analogy to somitogenesis—in which retinoic acid (RA) attenuation causes anterior somite pairs to develop L–R asynchronously—that RA pathway perturbation would likewise result in asymmetric mammary development. To test this, mammary glands of RXRα +/− mice were quantitatively assessed to compare left- versus right-side ductal epithelial networks. Unlike wild-type controls, half of the RXRα +/− thoracic mammary gland (TMG) pairs exhibited significant L–R asymmetry, with left-side reduction in network size. In RXRα +/− TMGs in which symmetry was maintained, networks had bilaterally increased size, with left networks showing greater variability in area and pattern. Reminiscent of posterior somites, whose bilateral symmetry is refractory to RA attenuation, inguinal mammary glands (IMGs) also had bilaterally increased network size, but no loss of symmetry. Together, these results demonstrate that mammary glands exhibit differential A–P sensitivity to RXRα heterozygosity, with ductal network symmetry markedly compromised in anterior but not posterior glands. As TMGs more closely model human breast development than IMGs, these findings raise the possibility that for some women, breast cancer risk may initiate with subtle axial patterning defects that result in L–R asymmetric growth and pattern of the mammary ductal epithelium. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’.


2012 ◽  
Vol 79 (2) ◽  
pp. 157-167 ◽  
Author(s):  
Lucile Yart ◽  
Laurence Finot ◽  
Pierre-Guy Marnet ◽  
Frédéric Dessauge

The objective of this study was to provide insight into the biological mechanisms underlying mammary development and the role of the ovaries in prepubertal caprine mammogenesis using a serial ovariectomy approach. Young Alpine goats were ovariectomized (Ovx) or sham-operated (Int) at three periods before puberty (G1=1 month, G2=2 month and G3=3 months of age) and one after puberty (G7=7 months of age). The goats were slaughtered at 9 months of age and mammary glands were removed. Ovariectomy performed at 1, 2 and 3 months of age caused a 50% reduction in DNA concentration, in mammary tissue taken from the parenchyma-stroma border region. Morphological analysis of mammary tissue sections indicated that the parenchymal structures of Ovx goats were negatively affected by ovariectomy. Goats ovariectomized before 2 months of age (Ovx-1 and Ovx-2) showed a significant decrease in the percent of cells proliferating in mammary glands of 9-month old goats (proliferating cell nuclear antigen expression and antigen Ki67-positive cell number). Also, goats ovariectomized at 1 and 2 months of age had reduced matrix metalloprotease 2 activity at 9 months of age. E-cadherin was strongly decreased in goats ovariectomized before 2 months of age (80 and 85% in Ovx-1 and Ovx-2 goats, respectively). Quantitative PCR analysis of transcripts encoding for oestrogen (ERα) and progesterone receptors (PR) and immunodetection of ERα showed that ovariectomy at 1 and 2 months of age strongly inhibited the transcription of ERα and PR in the mammary gland. We conclude that ovariectomy before 3 months of age markedly impaired parenchymal development. These findings suggest that prepubertal mammogenesis in goats depends on the ovaries to initiate mammary epithelial cell proliferation and mammary gland remodelling.


Author(s):  
Grace E. Berryhill ◽  
Julia M. Gloviczki ◽  
Josephine F. Trott ◽  
Jana Kraft ◽  
Adam L. Lock ◽  
...  

AbstractWe previously showed that dietary trans-10, cis-12 conjugated linoleic acid (10,12 CLA) stimulates estrogen-independent mammary growth in young ovariectomized mice. Here we investigated the effects of in utero or postnatal exposure to cis-9, trans-11 (9,11 CLA) and 10,12 CLA on postnatal development of the mammary gland and its responsiveness to ovarian steroids. In the first experiment we fed dams different CLA prior to and during gestation, then cross fostered female pups onto control fed dams prior to assessing the histomorphology of their mammary glands. Pregnant dams in the second experiment were similarly exposed to CLA, after which their female pups were ovariectomized then treated with 17β-estradiol (E), progesterone (P) or E + P for 5 days. In a third experiment, mature female mice were fed different CLA for 28 days prior to ovariectomy, then treated with E, P or E + P. Our data indicate that 10,12 CLA modifies the responsiveness of the mammary glands to E or E + P when exposure occurs either in utero, or postnatally. These findings underline the sensitivity of the mammary glands to dietary fatty acids and reinforce the potential for maternal nutrition to impact postnatal development of the mammary glands and their risk for developing cancer.


Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4547-4557 ◽  
Author(s):  
Elizabeth Tonner ◽  
Michael C. Barber ◽  
Gordon J. Allan ◽  
James Beattie ◽  
John Webster ◽  
...  

We have previously demonstrated that IGFBP-5 production by mammary epithelial cells increases dramatically during involution of the mammary gland. To demonstrate a causal relationship between IGFBP-5 and cell death we created transgenic mice expressing IGFBP-5 in the mammary gland using a mammary-specific promoter, β-lactoglobulin. DNA content in the mammary glands of transgenic mice was decreased as early as day 10 of pregnancy. Histological analysis indicated reduced numbers of alveolar end buds, with decreased ductal branching. Transgenic dams produced IGFBP-5 in their milk at concentrations similar to those achieved at the end of normal lactation. Mammary cell number and milk synthesis were both decreased by approximately 50% during the first 10 days of lactation. BrdU labelling was decreased, whereas DNA ladders were increased in transgenic animals on day 1 of lactation. On day 2 postpartum, the epithelial invasion of the mammary fat pad was clearly impaired in transgenic animals. The concentrations of the pro-apoptotic molecule caspase-3 and of plasmin were both increased in transgenic animals whilst the concentrations of 2 prosurvival molecules Bcl-2 and Bcl-xLwere both decreased. In order to examine whether IGFBP-5 acts by inhibiting the survival effect of IGF-I we examined IGF receptor phosphorylation and Akt phosphorylation and showed that both were inhibited. We attempted to “rescue” the transgenic phenotype by using growth hormone to increase endogenous IGF-I concentrations or by implanting minipumps delivering an IGF-1 analogue, R3-IGF-1, which binds weakly to IGFBP-5. Growth hormone treatment failed to affect mammary development suggesting that increased concentrations of endogenous IGF-1 are insufficient to overcome the high concentrations of IGFBP-5 produced by these transgenic animals. In contrast mammary development (gland weight and DNA content) was normalised by R3-IGF-I although milk production was only partially restored. This is the first demonstration that over-expression of IGFBP-5 can lead to; impaired mammary development, increased expression of the pro-apoptotic molecule caspase-3, increased plasmin generation and decreased expression of pro-survival molecules of the Bcl-2 family. It clearly demonstrates that IGF-I is an important developmental/survival factor for the mammary gland and, furthermore, this cell death programme may be utilised in a wide variety of tissues.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Jun-Fei Zhang ◽  
Jia Liu ◽  
Guo-Hua Gong ◽  
Bin Zhang ◽  
Cheng-Xi Wei

Mongolian medicine RuXian-I is composed of 30 Mongolian herbs, which is a traditional Mongolian recipe for clinical treatment of breast “Qi Su Bu Ri Le Du Sen” disease (hyperplasia of mammary glands, HMG). Based on the previous study, this dissertation further explores the therapeutic mechanism of RuXian-I on estrogen-induced HMG in rats. RuXian-I had no effect on the body weight and food intake of HMG rats and had no toxic effects on the five organs (heart, lung, spleen, and kidney). RuXian-I reduced the diameter and height of nipple, organ index, and pathological changes and alleviated the sex hormone levels oh HMG; RuXian-I reduced the upregulation of TCTP, Mcl-1, and Bcl-xL in breast tissue of mammary gland hyperplasia and increased the downregulation of p53, Bax, caspase-9, and caspase-3 protein. RuXian-I has an effective therapeutic activity on HMG rats, and its possible therapeutic mechanism is closely related to antiapoptosis protein TCTP-regulated apoptosis.


1962 ◽  
Vol 25 (3) ◽  
pp. 375-385 ◽  
Author(s):  
G. B. SHARMAN

SUMMARY The mammary glands of the marsupial Trichosurus vulpecula (the brush possum) showed a cycle of development and regression correlated with the oestrous cycle. Mammary glands of pregnant females were not significantly heavier than those of non-pregnant females at comparable times after oestrus. There were no clear differences in histology between mammary glands of mated and non-mated females at the same number of days after oestrus until the 17th day. At this time the mammary glands of three non-mated females were clearly different from the glands of three post-partum females. Lactation was initiated in six out of eight non-mated females, including one virgin female, by transferring newborn young, which attached themselves to teats, to their pouches. Of the six transferred young which attached all, except one, lived and showed normal growth. The rate of regression of previously suckled mammary glands was slower in lactating than in non-lactating females. No clear evidence was obtained of hypertrophy of the non-suckled mammary gland following the attachment of a single young to the teat of the alternate mammary gland. However, the micro-anatomy of the non-suckled gland at 8 days after the onset of lactation suggested that milk may have distended the alveoli. These observations are discussed in relation to the control of lactation in the female marsupial. It is suggested that, in marsupials, the hormones circulating during the oestrous cycle cause full mammary development and that the suckling stimulus of the newborn young is sufficient to initiate lactation. The yolk-sac placenta of the brush possum apparently plays no essential part in mammary gland development. Otherwise the pattern of lactation in the brush possum does not appear to differ from that of eutherian mammals.


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