scholarly journals Differential Hormonal Regulation and Function of Progesterone Receptor Isoforms in Normal Adult Mouse Mammary Gland

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2290-2300 ◽  
Author(s):  
Mark D. Aupperlee ◽  
Sandra Z. Haslam
Keyword(s):  
Mammary Gland ◽  
Hormonal Regulation ◽  
Adult Mouse ◽  
Mouse Mammary Gland ◽  
Functional Roles ◽  
Progesterone Receptor Isoforms ◽  
Receptor Isoforms ◽  
Mitogenic Action ◽  
And Function

In normal mouse mammary gland, the mitogenic action of progesterone (P) is mediated by two P receptor (PR) isoforms, PRA and PRB. PRA is predominantly expressed in the adult virgin, and PRB is predominantly expressed during pregnancy. To investigate hormonal regulation of PR isoform expression and isoform-specific functions in vivo, adult ovariectomized BALB/c mice were treated for 3, 5, or 10 d with estrogen (E), P, or estrogen plus progesterone (E+P). Using an immunohistochemical approach with isoform-specific antibodies, we investigated hormonal regulation of PRA and PRB and their functional roles in proliferation and morphogenesis. Significant E-induced proliferation was only observed after 5 d at the distal tips of ducts; there was no sidebranching or alveologenesis. P induced proliferation that resulted in sidebranching and alveologenesis, but E+P treatment produced more proliferation sooner and more extensive sidebranching and alveologenesis. PRA levels were increased by E and decreased by P. Increased PRB levels were induced by treatment with P or E+P and coincided with the formation of alveoli. PRA was the predominant PR isoform expressed during sidebranching, and colocalization of PRA with 5-bromo-2′-deoxyuridine revealed that proliferation of PRA-positive and -negative cells was responsible for P-induced sidebranching. PRB was the predominant PR isoform expressed during alveologenesis, and colocalization of PRB with 5-bromo-2′-deoxyuridine showed that both PRB-positive and -negative cells proliferated during alveolar expansion. These results demonstrate different hormonal regulation of PRA and PRB levels in vivo and suggest that P can induce proliferation through either PRA or PRB via direct and paracrine mechanisms.

HORMONAL REGULATION OF RNA AND PROTEIN SYNTHESIS IN THE MOUSE MAMMARY GLAND BEFORE AND DURING LACTATION

1971 ◽  
Vol 50 (2) ◽  
pp. 281-291 ◽  
Author(s):  
M. R. BANERJEE ◽  
FERNE M. ROGERS ◽  
D. N. BANERJEE
Keyword(s):  
Protein Synthesis ◽  
Mammary Gland ◽  
Hormonal Regulation ◽  
Rna Synthesis ◽  
Mouse Mammary Gland ◽  
Synthetic Activity ◽  
Tissue Homogenate ◽  
Mammary Tissue ◽  
Leucine Incorporation

SUMMARY As measured by [3H]uridine incorporation in vivo, the low rate of RNA synthesis in the mammary gland of virgin C3H and BALB/c mice increased sixfold in the mammary tissue of 15-day pregnant mice. In the 5-day lactating gland, RNA synthesis was ten times higher than that in virgin mammary tissue. On the 10th day of lactation this increased RNA synthetic activity in the mammary gland was considerably reduced but was still twice that of the mammary tissue of virgin mice. Twenty-four hours after adrenalectomy, RNA synthesis in lactating glands was reduced by over 80%, whereas in the mammary gland before lactation, it was reduced by 20–30% only. A single i.p. injection of 250 μg of cortisol led to a threefold increase of RNA synthesis within 1 to 2 h in lactating glands of adrenalectomized mice; this was followed by a decline. Incorporation of [3H]leucine into trichloroacetic acid-insoluble material from lactating mammary tissue was used as a measure of'total protein' synthesis, and [3H]leucine radioactivity determined in Ca2+−rennin precipitate of 105000 g supernatant of lactating mammary tissue homogenate was used as a measure of casein synthesis. Adrenalectomy caused a 50% reduction of 'total protein' synthesis, whereas synthesis of 'casein-like' phosphoprotein virtually stopped after the operation. The injection of cortisol into adrenalectomized mice induced a selective increase of [3H]leucine incorporation into the casein of lactating glands. The results indicate that RNA synthesis in the mammary tissue is more dependent on adrenal hormones during the functional than the structural state of differentiation. The hormonal regulation of RNA synthesis and its role in milk protein synthesis in the mammary gland in vivo is discussed.

scholarly journals In vivo MRI of early stage mammary cancers and the normal mouse mammary gland

2011 ◽  
Vol 24 (7) ◽  
pp. 880-887 ◽  
Author(s):  
Sanaz A. Jansen ◽  
Suzanne D. Conzen ◽  
Xiaobing Fan ◽  
Erica Markiewicz ◽  
Thomas Krausz ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Normal Mouse ◽  
Early Stage ◽  
Mouse Mammary Gland

scholarly journals 220- and 130-kDa MLCKs have distinct tissue distributions and intracellular localization patterns

2002 ◽  
Vol 282 (3) ◽  
pp. C451-C460 ◽  
Author(s):  
Emily K. Blue ◽  
Zoe M. Goeckeler ◽  
Yijun Jin ◽  
Ling Hou ◽  
Shelley A. Dixon ◽  
...  
Keyword(s):  
Intracellular Trafficking ◽  
Myosin Light Chain ◽  
Adult Mouse ◽  
Intracellular Localization ◽  
Myosin Ii ◽  
Nonmuscle Myosin ◽  
Functional Roles ◽  
Nonmuscle Myosin Ii ◽  
Mouse Tissues

To better understand the distinct functional roles of the 220- and 130-kDa forms of myosin light chain kinase (MLCK), expression and intracellular localization were determined during development and in adult mouse tissues. Northern blot, Western blot, and histochemical studies show that the 220-kDa MLCK is widely expressed during development as well as in several adult smooth muscle and nonmuscle tissues. The 130-kDa MLCK is highly expressed in all adult tissues examined and is also detectable during embryonic development. Colocalization studies examining the distribution of 130- and 220-kDa mouse MLCKs revealed that the 130-kDa MLCK colocalizes with nonmuscle myosin IIA but not with myosin IIB or F-actin. In contrast, the 220-kDa MLCK did not colocalize with either nonmuscle myosin II isoform but instead colocalizes with thick interconnected bundles of F-actin. These results suggest that in vivo, the physiological functions of the 220- and 130-kDa MLCKs are likely to be regulated by their intracellular trafficking and distribution.

scholarly journals The STAGA Subunit ADA2b Is an Important Regulator of Human GCN5 Catalysis

2008 ◽  
Vol 29 (1) ◽  
pp. 266-280 ◽  
Author(s):  
Armin M. Gamper ◽  
Jaehoon Kim ◽  
Robert G. Roeder
Keyword(s):  
Saga Complex ◽  
Histone Tails ◽  
Functional Roles ◽  
Enzymatic Function ◽  
Core Histones ◽  
Human Proteins ◽  
Important Regulator ◽  
And Function

ABSTRACT Human STAGA is a multisubunit transcriptional coactivator containing the histone acetyltransferase GCN5L. Previous studies of the related yeast SAGA complex have shown that the yeast Gcn5, Ada2, and Ada3 components form a heterotrimer that is important for the enzymatic function of SAGA. Here, we report that ADA2a and ADA2b, two human homologues of yeast Ada2, each have the ability to form a heterotrimer with ADA3 and GCN5L but that only the ADA2b homologue is found in STAGA. By comparing the patterns of acetylation of several substrates, we found context-dependent requirements for ADA2b and ADA3 for the efficient acetylation of histone tails by GCN5. With human proteins, unlike yeast proteins, the acetylation of free core histones by GCN5 is unaffected by ADA2b or ADA3. In contrast, the acetylation of mononucleosomal substrates by GCN5 is enhanced by ADA2b, with no significant additional effect of ADA3, and the efficient acetylation of nucleosomal arrays (chromatin) by GCN5 requires both ADA2b and ADA3. Thus, ADA2b and ADA3 appear to act at two different levels of histone organization within chromatin to facilitate GCN5 function. Interestingly, although ADA2a forms a complex(es) with GCN5 and ADA3 both in vitro and in vivo, ADA2a-containing complexes are unable to acetylate nucleosomal H3. We have also shown the preferential recruitment of ADA2b, relative to ADA2a, to p53-dependent genes. This finding indicates that the previously demonstrated presence and function of GCN5 on these promoters reflect the action of STAGA and that the ADA2a and ADA2b paralogues have nonredundant functional roles.

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