Aryl hydrocarbon (benzo[a]pyrene) hydroxylase in rat mammary tissue during pregnancy and lactation

1979 ◽  
Vol 57 (1) ◽  
pp. 112-117 ◽  
Author(s):  
Jacquelene M. Fysh ◽  
Allan B. Okey

Rats are highly resistant to mammary tumour induction by polycyclic aromatic hydrocarbons during pregnancy and lactation. Since local changes in hydrocarbon metabolism in mammary tissue or altered hepatic metabolism might contribute to the resistance, aryl hydrocarbon hydroxylase (AHH) activity in microsomes from mammary tissue and liver was measured throughout the course of pregnancy and lactation in Sprague–Dawley rats. Basal constitutive AHH activity in mammary tissue and liver of untreated rats did not change significantly during pregnancy or lactation. In rats injected with beta-naphthoflavone (BNF), AHH activity in liver microsomes increased approximately 25-fold over basal levels and the degree of enzyme induction by BNF was relatively constant throughout pregnancy and lactation. In mammary tissue, however, the induction of AHH by BNF increased dramatically from about 10 times basal at the beginning of pregnancy to over 80 times basal on day 3 of lactation. The high inducibility of mammary AHH during late pregnancy and early lactation exists both when activity is expressed per unit microsomal protein or per unit tissue DNA. Increased inducibility of mammary AHH may contribute to the resistance rats show to hydrocarbon carcinogenesis during pregnancy and lactation. Since the activity of hepatic AHH does not change significantly during pregnancy or lactation, it seems unlikely that resistance is due to altered hepatic metabolism of the hydrocarbons. AHH activity can be associated both with 'metabolic activation' and 'detoxification' of aromatic hydrocarbons. The balance between local 'activation' and 'detoxification' of aromatic hydrocarbons by AHH in mammary tissue during different physiological states is important in determining susceptibility to carcinogenesis and requires further study.

1993 ◽  
Vol 9 (3) ◽  
pp. 503-509 ◽  
Author(s):  
Juergen Fuchs ◽  
Jiri Mlcoch ◽  
Franz Oesch ◽  
Karl Ludwig Platt

Two highly polar DNA adducts were found after metabolic activation of 3,4,10,11-tetrahydroxy-3,4,10,11-tetrahydrodibenz[ a,h]anthracene(DBA-3,4;10, 11-bisdiol) by liver microsomes isolated from male Sprague-Dawley rats pretreated with Aroclor 1254 in presence of calf thymus DNA. These DNA adducts could be assigned to the metabolites of dibenz[ a,h]anthracene (DBA), of 3R,4R,10R,11R-tetrahydroxy-3,4,10,11-tetrahydro-DBA and of 3R,4R,10S,US-tetrahydroxy-3,4,10,11-tetrahydro-DBA. DNA adducts derived from metabolites of 3S,4S,10S,11S-tetrahydroxy-3,4,10,11-tetrahydro-DBA were not found. These highly polar adducts also could be detected by reversed phase HPLC after incubation of dibenz[ a,h]anthracene, 3R,4R-dihydroxy-3,4-dihydro-DBA ((-)-DBA-3,4-diol) and 3S,4S- dihydroxy-3,4-dihydro-DBA ((+)-DBA-3,4-diol) with DNA in presence of the activating system. After incubation of 14C labelled DBA DNA adducts derived from DBA-3,4;10,11-bisdiol were found in a fraction of 38% and bay region 3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydro-DBA-DNA adducts at a level of 25%. DBA-3,4; 10,11-bisdiol exhibited a higher DNA binding yield (38 × 12 pmollmg DNA) than (-)-DBA-3,4-diol (23 × 6 pmol/mg DNA), the most mutagenic 3,4-diol enantiomer. For (+)-DBA-3,4-diol the highly polar DNA adducts derived from DBA-3,4;10,11-bisdiol were by far the most predotmnant adducts in vitro.


1974 ◽  
Vol 62 (2) ◽  
pp. 213-223 ◽  
Author(s):  
SAKAE KIKUYAMA ◽  
HIROSHI NAGASAWA ◽  
REIKO YANAI ◽  
KOREHITO YAMANOUCHI

SUMMARY Female Sprague—Dawley rats were fed 6-propyl-2-thiouracil (PTU) in their diet during late pregnancy and lactation. The growth and gonadal development of their pups were inhibited and in females the day of vaginal opening and onset of oestrous cycles were delayed; thyroid glands were hypertrophied. Treatment of the pups with thyroxine largely reversed these changes. The effect on body weight persisted even after treatment with PTU had stopped. At 20 days of age, the anterior pituitary glands of the pups of PTU-treated mothers contained significantly less growth hormone (GH) and prolactin than those of normal pups of both sexes. These changes persisted at 60 days of age. If the pups of PTU-treated mothers were given thyroxine from day 1 to day 20 of age, pituitary GH and prolactin content on day 20 had returned towards normal values. Thyroid deficiency was found to suppress the synthesis and release of prolactin and the synthesis of GH by the pituitary in vitro. These findings suggest that thyroxine influenced the maturation of the pituitary directly and/or through the hypothalamus and that thyroxine deficiency in early life brought about persistent alteration of the pituitary secretion of GH and prolactin.


1992 ◽  
Vol 263 (6) ◽  
pp. E1077-E1085 ◽  
Author(s):  
M. Rakopoulos ◽  
S. J. Vargas ◽  
M. T. Gillespie ◽  
P. W. Ho ◽  
H. Diefenbach-Jagger ◽  
...  

Production of parathyroid hormone-related protein by the rat mammary gland in pregnancy and lactation. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E1077-E1085, 1992.--Production of parathyroid hormone-related protein (PTHrP) by the mammary gland of Sprague-Dawley rats has been examined using immunohistochemistry and in situ hybridization to detect PTHrP and PTHrP mRNA, respectively. PTHrP and PTHrP mRNA could be demonstrated in nests of epithelial cells of the developing mammary gland at day 14 of pregnancy and in the epithelial secretory cells lining the alveoli during the latter stages of pregnancy and during lactation. A specific radioimmunoassay was also used to measure the concentration of PTHrP secreted in the milk throughout lactation. The concentration of PTHrP in milk was relatively low initially but increased during the latter stages of lactation, whereas calcium concentrations remained virtually constant throughout lactation. No correlation was found between the concentrations of calcium and PTHrP in rat milk. These results show that PTHrP is present in rat milk and also in mammary tissue before parturition, and therefore it may assist in the development of the mammary gland during pregnancy.


2020 ◽  
Vol 176 (1) ◽  
pp. 46-64 ◽  
Author(s):  
Michael A Garland ◽  
Mitra C Geier ◽  
Sean M Bugel ◽  
Prarthana Shankar ◽  
Cheryl L Dunham ◽  
...  

Abstract The aryl hydrocarbon receptor (AHR) mediates developmental toxicity of several xenobiotic classes including polycyclic aromatic hydrocarbons. Using embryonic zebrafish, we previously identified 4 polycyclic aromatic hydrocarbons that caused a novel phenotype among AHR ligands—growth of a lateral, duplicate caudal fin fold. The window of sensitivity to the most potent inducer of this phenotype, benzo[k]fluoranthene (BkF), was prior to 36 h postfertilization (hpf), although the phenotype was not manifest until 60 hpf. AHR dependency via Ahr2 was demonstrated using morpholino knockdown. Hepatocyte ablation demonstrated that hepatic metabolism of BkF was not required for the phenotype, nor was it responsible for the window of sensitivity. RNA sequencing performed on caudal trunk tissue from BkF-exposed animals collected at 48, 60, 72, and 96 hpf showed upregulation of genes associated with AHR activation, appendage development, and tissue patterning. Genes encoding fibroblast growth factor and bone morphogenic protein ligands, along with retinaldehyde dehydrogenase, were prominently upregulated. Gene Ontology term analysis revealed that upregulated genes were enriched for mesoderm development and fin regeneration, whereas downregulated genes were enriched for Wnt signaling and neuronal development. MetaCore (Clarivate Analytics) systems analysis of orthologous human genes predicted that R-SMADs, AP-1, and LEF1 regulated the expression of an enriched number of gene targets across all time points. Our results demonstrate a novel aspect of AHR activity with implications for developmental processes conserved across vertebrate species.


2006 ◽  
Vol 263 (6) ◽  
pp. E1077-E1085 ◽  
Author(s):  
M. Rakopoulos ◽  
S. J. Vargas ◽  
M. T. Gillespie ◽  
P. W. Ho ◽  
H. Diefenbach-Jagger ◽  
...  

Production of parathyroid hormone-related protein by the rat mammary gland in pregnancy and lactation. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E1077-E1085, 1992.--Production of parathyroid hormone-related protein (PTHrP) by the mammary gland of Sprague-Dawley rats has been examined using immunohistochemistry and in situ hybridization to detect PTHrP and PTHrP mRNA, respectively. PTHrP and PTHrP mRNA could be demonstrated in nests of epithelial cells of the developing mammary gland at day 14 of pregnancy and in the epithelial secretory cells lining the alveoli during the latter stages of pregnancy and during lactation. A specific radioimmunoassay was also used to measure the concentration of PTHrP secreted in the milk throughout lactation. The concentration of PTHrP in milk was relatively low initially but increased during the latter stages of lactation, whereas calcium concentrations remained virtually constant throughout lactation. No correlation was found between the concentrations of calcium and PTHrP in rat milk. These results show that PTHrP is present in rat milk and also in mammary tissue before parturition, and therefore it may assist in the development of the mammary gland during pregnancy.


1990 ◽  
Vol 4 (2) ◽  
pp. 101-106 ◽  
Author(s):  
F. F. Bolander ◽  
M. E. Blackstone

ABSTRACT A radioimmunoassay was developed and validated for the major glycoprotein (gp58) of the mouse mammary tumour virus (MMTV). Using this assay, the expression of gp58 during pregnancy and lactation was found to parallel that for MMTV RNA. In particular, there was a very rapid induction in late pregnancy and a decline in late lactation, although some residual expression persisted well into involution. In cultures of normal mouse mammary tissue, induction of gp58 occurred after a 24-h lag period and began to reach a plateau after 3 days. Both the insulin and prolactin dose—response curves for gp58 resembled those for MMTV RNA; in contrast, the effects of steroid hormones on gp58 and MMTV RNA were disparate. Although progesterone stimulated the RNA, it only slightly increased gp58 levels; however, the presence of cortisol greatly augmented this stimulation, despite the inability of cortisol to induce RNA at physiological concentrations. These results suggest that insulin, prolactin and progesterone act primarily at the level of RNA accumulation in normal mammary epithelium, while cortisol affects some more distal event.


2008 ◽  
Vol 10 (5) ◽  
pp. 466-471 ◽  
Author(s):  
Rita Payan-Carreira ◽  
Ana C. Martins-Bessa

The aim of this study is to characterise the feline mammary echotexture using B-mode ultrasonography, which is not routinely used to examine the feline mammary gland. Using a 5–9 MHz linear transducer the ultrasonographic appearance of non-stimulated and stimulated mammary glands was determined in 35 mature intact non-pregnant, pregnant and lactating queens aged from 16 months to 8 years. In intact non-pregnant queens, mammary glands are fairly underdeveloped and on the ultrasonograms they appear with a regular hypoechoic texture and generally show a thickness of less than 2.0 mm. The stimulated mammary tissue typically presents a more hyperechoic appearance compared to the non-stimulated gland and a fine granular echotexture. Maximum echogenicity of the mammary gland is reached during lactation. In late pregnancy, the mammary glands reach 6–9 mm in thickness. During lactation, the size of the glands depends on the existence of a suckling stimulus, with the suckled glands reaching about 11 mm in thickness. Ductal structures can only be imaged during late pregnancy and lactation. Ultrasonographic evaluation of the feline mammary gland can become a valuable diagnostic tool to characterise physiological changes and may further contribute to a better characterisation of diseased mammary tissue.


Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1393
Author(s):  
Chien-Ning Hsu ◽  
Chih-Hsing Hung ◽  
Chih-Yao Hou ◽  
Chi-I. Chang ◽  
You-Lin Tain

Exposure to environmental chemicals during pregnancy and lactation is a contributing factor in gut microbiota dysbiosis and linked to programming of hypertension. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin, induces toxic effects by mediating aryl hydrocarbon receptor (AHR). Resveratrol, a potent antioxidant with prebiotic properties, can possess high affinity for AHR and protect against TCDD-activated AHR attack. We examined whether perinatal resveratrol therapy prevents offspring hypertension programmed by maternal TCDD exposure and whether its beneficial effects are related to reshaping gut microbiota and antagonizing AHR-mediated T helper 17 (TH17) cells responses using a maternal TCDD exposure rat model. Pregnant Sprague-Dawley rats were given a weekly oral dose of TCDD 200 ng/kg for four doses (T), 50 mg/L of resveratrol in drinking water (CR), TCDD + resveratrol (TR), or vehicle (C) in pregnancy and lactation periods. Male offspring (n = 7–8/group) were sacrificed at the age of 12 weeks. Perinatal TCDD exposure caused elevated blood pressure in adult male offspring, which resveratrol supplementation prevented. Additionally, the TCDD-induced programming of hypertension is coincided with the activation of AHR signaling, TH17-induced renal inflammation, and alterations of gut microbiota compositions. Conversely, TCDD-mediated induction of AHR signaling and TH17 responses were restored by maternal resveratrol supplementation. Furthermore, maternal resveratrol supplementation prevented the programming of hypertension and was related to increased genera Bacteroides, ASF356, and Lachnoclostridium. Taken together, these results suggest that the interplay between gut microbiota, AHR-mediated TH17 responses, and renal inflammation in the gut and kidneys may play an important role in the action of resveratrol against TCDD-induced programming of hypertension.


2014 ◽  
Vol 46 (15) ◽  
pp. 560-570 ◽  
Author(s):  
A. M. Paten ◽  
S. J. Pain ◽  
S. W. Peterson ◽  
H. T. Blair ◽  
P. R. Kenyon ◽  
...  

The mammary gland is a complex tissue consisting of multiple cell types which, over the lifetime of an animal, go through repeated cycles of development associated with pregnancy, lactation and involution. The mammary gland is also known to be sensitive to maternal programming by environmental stimuli such as nutrition. The molecular basis of these adaptations is of significant interest, but requires robust methods to measure gene expression. Reverse-transcription quantitative PCR (RT-qPCR) is commonly used to measure gene expression, and is currently the method of choice for validating genome-wide expression studies. RT-qPCR requires the selection of reference genes that are stably expressed over physiological states and treatments. In this study we identify suitable reference genes to normalize RT-qPCR data for the ovine mammary gland in two physiological states; late pregnancy and lactation. Biopsies were collected from offspring of ewes that had been subjected to different nutritional paradigms during pregnancy to examine effects of maternal programming on the mammary gland of the offspring. We evaluated eight candidate reference genes and found that two reference genes ( PRPF3 and CUL1) are required for normalising RT-qPCR data from pooled RNA samples, but five reference genes are required for analyzing gene expression in individual animals ( SENP2, EIF6, MRPL39, ATP1A1, CUL1). Using these stable reference genes, we showed that TET1, a key regulator of DNA methylation, is responsive to maternal programming and physiological state. The identification of these novel reference genes will be of utility to future studies of gene expression in the ovine mammary gland.


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