Mammary tissue

Many human diseases are caused when certain proteins are either over- or underexpressed. Eor example, breast cancer can be induced by overexpressing certain cellular oncogenes within mammary tissue. To study the disease, researchers produce a line of transgenic mice that synthesize an abnormal amount of the same protein. This leads to symptoms of the disease in mice that are similar to what is found in humans. A protein can be overexpressed by inserting a DNA constmct with a strong promotor. Conversely, underexpression of a protein can be achieved by inserting a DNA constmct that makes antisense RNA. This latter blocks protein synthesis because the antisense RNA binds and inactivates the sense mRNA that codes for the protein. Once a line of mice is developed, treatments are studied in mice before these therapies are appHed to humans. 

Concha, C. (1986), Cell types and their immunological functions in bovine mammary tissues and secretions - a review of literature . Nordisk Veterinaermedicin, 38, 257-272. 

The carcinogenicity of a series of PAH in the mammary gland has been examined in 50-day-old female Sprague-Dawley rats using direct application of the compound to the mammary tissue (1 , 17, 18). The results of these experiments, presented in Table III, are compared to the carcinogenicity results in mouse skin from repeated application obtained in our laboratory and others. PAH were selected because they were or were not expected to be activated by one-electron oxidation, based on the hypothesis that compounds with relatively high IP cannot be activated by this mechanism. Furthermore, some... 

Estradiol. The first neuroactive steroid receptor type to be recognized was that for estradiol [3]. In vivo uptake of [3H] estradiol, and binding to cell nuclei isolated from hypothalamus, pituitary and other brain regions, revealed steroid specificity closely resembling that of the uterus, where steroid receptors were first discovered [3]. Cytosolic estrogen receptors isolated from pituitary and brain tissue closely resemble those found in uterus and mammary tissue. A hallmark of the estrogen receptor is its existence... 

Compound Mammary tissue Uterus metabolism Bone Cholesterol... 

Similarly, the 4-methoxy-2-naphthylamides of Leu, Ala, Arg, and Glu (6.1, R=side chain of amino acid, R =MeO) were used to assess the type and activity of aminopeptidase in homogenates of conjunctival, nasal, buccal, duodenal, ileal, rectal, and vaginal tissues from rabbits. This systematic comparison afforded a better understanding of the role of the aminopeptidase barrier in peptide absorption from oral vs. non-oral routes [18]. In a comparable manner, the y-glutamyltranspeptidase and dipeptidase activities were investigated in mammary tissue with the 4-nitroanilides of Leu, Met, Lys, Glu, and Asp (6.2, R=side chain of amino acid) [19]. 

D. B. Shennan, F. R. C. Backwell, D. T. Calvert, Metabolism of Aminoacyl-p-nitroan-ilides by Rat Mammary Tissue , Biochim. Biophys. Acta 1999, 1427, 227-235. 

Breast milk During lactation human mammary tissue expresses the sodium iodide symporter [260], and thus significant transfer of perchlorate into human milk is likely. The presence of micrograms per liter concentrations of perchlorate in milk collected fi om US women [233] confirms lactation as a relevant perchlorate excretion path. If lactating women are secreting perchlorate in milk, then urine-based estimates of total perchlorate exposure for these individuals are likely to be lower than actual [242]. 

Mammary tissue milk-producing tissue of the breast. 

Ruminant milk fats are also rich in medium-chain fatty acids. These are synthesized in the mammary gland via the usual malonyl CoA pathway (section 3.5) and are released from the synthesizing enzyme complex by thioacylases presumably, the higher levels of medium chain acids in ruminant milk fats compared with those of monogastric animals reflect higher thioacylase activity in the mammary tissue of the former. 

Synthesis of fatty acids via the malonyl CoA pathway does not proceed beyond palmitic acid (C16 0) and mammary tissue contains an enzyme, thioacylase, capable of releasing the acyl fatty acid from the carrier protein at any stage between C4 and C16. Probable interspecies differences in the activity of thioacylase may account for some of the interspecies differences in milk fatty acid profiles. 

Isolation and characterization. Alkaline phosphatase is concentrated in the fat globule membrane and hence in cream. It is released into the buttermilk on phase inversion consequently, buttermilk is the starting material for most published methods for the purification of alkaline phosphatase. Later methods have used chromatography on various media to give a homogeneous preparation with 7440-fold purification and 28% yield. The characteristics of milk alkaline phosphatase are summarized in Table 8.2. The enzyme appears to be similar to the alkaline phosphatase of mammary tissue. 

The synthesis of fatty acids for incorporation into milk fat within the mammary gland is similar to that seen in other tissues. There are two basic reactions the conversion of acetyl-coenzyme A (CoA) to malonyl-CoA, followed by incorporation of the latter into a growing acyl chain via the action of the fatty acid-synthetase complex. However, the product of these reactions in lactating mammary tissue from many species is short and medium chain fatty acids. In most other tissues the product is palmitate. For more complete details see Moore and Christie, (1978), Bauman and Davis (1974), and Patton and Jensen (1976). 

In the ruminant mammary tissue, it appears that acetate and /3-hydroxybutyrate contribute almost equally as primers for fatty acid synthesis (Palmquist et al. 1969 Smith and McCarthy 1969 Luick and Kameoka 1966). In nonruminant mammary tissue there is a preference for butyryl-CoA over acetyl-CoA as a primer. This preference increases with the length of the fatty acid being synthesized (Lin and Kumar 1972 Smith and Abraham 1971). The primary source of carbons for elongation is malonyl-CoA synthesized from acetate. The acetate is derived from blood acetate or from catabolism of glucose and is activated to acetyl-CoA by the action of acetyl-CoA synthetase and then converted to malonyl-CoA via the action of acetyl-CoA carboxylase (Moore and Christie, 1978). Acetyl-CoA carboxylase requires biotin to function. While this pathway is the primary source of carbons for synthesis of fatty acids, there also appears to be a nonbiotin pathway for synthesis of fatty acids C4, C6, and C8 in ruminant mammary-tissue (Kumar et al. 1965 McCarthy and Smith 1972). This nonmalonyl pathway for short chain fatty acid synthesis may be a reversal of the /3-oxidation pathway (Lin and Kumar 1972). 

Both goat and cow mammary tissue synthesize medium-chain fatty acids. However, attempts to isolate thioesterase II from the cytosol of ruminant mammary tissues have not been successful (Grunnet and Knudsen 1979). In contrast to the nonruminant, the fatty acid-... 

Knudsen and Grunnet (1982) have proposed an interesting system for the control of medium-chain fatty acid synthesis by ruminant mammary tissue. Their proposal is based on their observations that ruminant mammary tissue fatty acid-synthetase exhibits both medium-chain thioesterase (Grunnet and Knudsen 1978) and transacylase (Knudsen and Grunnet 1980) activity and that medium-chain fatty acids synthesized de novo can be incorporated into TG without an intermediate activation step (Grunnet and Knudsen 1981). They proposed that the synthesis of the medium-chain fatty acids is controlled by their incorporation into TG (Grunnet and Knudsen 1981). Further work will be needed to substantiate transacylation as a chain-termination mechanism in fatty acid synthesis by ruminant mammary tissue. 

The esterification of fatty acids in the mammary cell has been reported as a function of the microsomes and mitochondria (Bauman and Davis 1974 Moore and Christie 1978). While both microsomes and mitochondria may have acyltransferase activity, it has been observed to be 10 times greater in the microsomal fraction of the rat mammary cell (Tanioka et al. 1974). Based on autoradiographic studies, it appears that most synthesis of milk TG occurs in the rough endoplasmic reticulum of mouse mammary tissue (Stein and Stein 1971). 

In many in vitro studies the acylation of the sn-3 position appears to be the rate-limiting step in TG synthesis. It has been suggested that the intracellular concentration of medium chain fatty acids may limit the final acylation reaction in TG synthesis (Dimmena and Emery 1981). Another theory is that the concentration of phosphatidate phosphatase, the enzyme that hydrolyzes the phosphate bond in phospha-tidic acid, yielding DG, may be the limiting factor (Moore and Christie 1978). The DG acyltransferase responsible for the final acylation of milk TG has been studied in mammary tissue from lactating rats (Lin et al. 1976). It was observed to be specific for the sn-1,2 DG, with very little activity observed with the sn-1,3 or sn-2,3 DG. It exhibited a broad specificity for acyl donors. The acyl-CoA specificity was not affected by the type of 1,2 DG acceptor offered, which implies that the type of fatty acid introduced into the glycerol backbone was not influenced by the specificity of subsequent acylation steps. However, the concentration of acyl donors will affect the final acylation. It was ob-... 

Diphosphatidylglycerol (cardiolipin) was found in lactating mammary tissue at levels 200-300 times those found in milk (Patton et al. 1969). 

Keenan and Patton (1970) isolated and identified the cholesterol esters from cow, sow, and goat milk and mammary tissue. The fatty acid composition of the esters from the cow is presented in Table 4.11. The au-... 

Dimenna, G. P. and Emery, R. S. 1981. Palmitate and octanoate metabolism in bovine mammary tissue. J. Dairy Sci. 64, 132-134. 

Keenan, T. W. and Patton, S. 1970. Cholesterol esters of milk and mammary tissue. Lipids 5, 42-48. 

McCarthy, S. and Smith, G. H. 1972. Synthesis of milk from 0-hydroxybutyrate and acetate by ruminant mammary tissue in vitro. Biochim. Biophys. Acta 260, 185-196. 

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