Gland Growth In Mice Research Articles

Trans-Fatty Acid-Stimulated Mammary Gland Growth in Ovariectomized Mice is Fatty Acid Type and Isomer Specific.

We previously reported that the trans-18:2 fatty acid trans-10, cis-12 conjugated linoleic acid (t10,c12-CLA) stimulates mammary gland development independent of estrogen and its receptor. Given the negative consequences of dietary trans-fatty acids on various aspects of human health, we sought to establish whether other trans-fatty acids could similarly induce ovary-independent mammary gland growth in mice. Prepubertal BALB/cJ mice were ovariectomized at 21 days of age then were fed diets enriched with cis-9, trans-11 CLA (c9,t11-CLA), or mixtures of trans-18:1 fatty acids supplied by partially hydrogenated sunflower, safflower, or linseed oil. The resultant mammary phenotype was evaluated 3 weeks later and compared to the growth response elicited by t10,c12-CLA, or the defined control diet. Whereas partially hydrogenated safflower oil increased mammary gland weight, none of the partially hydrogenated vegetable oils promoted mammary ductal growth. Similarly, the c9,t11-CLA supplemented diet was without effect on mammary development. Taken together, our data emphasize a unique effect of t10,c12-CLA in stimulating estrogen-independent mammary gland growth manifest as increased mammary ductal area and elongation that was not recapitulated by c9,t11-CLA or the partially hydrogenated vegetable oil diets.

Cadmium Promotes Breast Cancer Cell Proliferation by Potentiating the Interaction between ERα and c-Jun

Cadmium is an environmental contaminant that enters the body through diet or cigarette smoke. It affects multiple cellular processes, including cell proliferation, differentiation, and apoptosis. Recently, cadmium has been shown to function as an endocrine disruptor, to stimulate estrogen receptor alpha (ERalpha) activity and promote uterine and mammary gland growth in mice. Although cadmium exposure has been associated with the development of breast cancer, the mechanism of action of cadmium remains unclear. To address this deficit, we examined the effects of cadmium treatment on breast cancer cells. We found that ERalpha is required for both cadmium-induced cell growth and modulation of gene expression. We also determined that ERalpha translocates to the nucleus in response to cadmium exposure. Additionally, we provide evidence that cadmium potentiates the interaction between ERalpha and c-Jun and enhances recruitment of this transcription factor complex to the proximal promoters of cyclin D1 and c-myc, thus increasing their expression. This study provides a mechanistic link between cadmium exposure and ERalpha and demonstrates that cadmium plays an important role in the promotion of breast cancer.

Decreased p44/42 Mitogen-Activated Protein Kinase Phosphorylation in Gender- or Hormone-Related But Not during Age-Related Adrenal Gland Growth in Mice

Postnatal growth of the mouse adrenal gland shows a characteristic gender-dependent pattern, resulting in an almost 2-fold higher adrenal weight in 11-wk-old female vs. male mice. We demonstrated that the higher weight of the adrenal glands in female mice is due to a significantly (P < 0.05) increased growth rate in female mice and a shorter growth phase of the adrenal glands in male mice (P < 0.05). To address the signaling mechanisms underlying these differential growth patterns, we evaluated the phosphorylation levels of p44/42 and p38 MAPK. In female mice, age-dependent reductions of p38 MAPK phosphorylation were found between wk 3 and 9 (47% reduction; P < 0.05). At the age of 11 wk, the p38 MAPK phosphorylation level in female adrenal glands was about 60% lower than in the male counterparts (P < 0.01). Similarly, the phosphorylation level of p44/42 MAPK was 50% lower in female adrenal glands (P < 0.001). Reduced activation of p44/42 MAPK was also observed after growth stimulation of the adrenal glands in male mice after ACTH treatment (-36%; P < 0.001) or by expression of a GH transgene (-34%; P < 0.001), whereas p38 MAPK, JNK, or PDK1 activation was unaffected. From our findings in three independent mouse models where partial deactivation of p44/42 MAPK was observed under conditions of elevated growth, we suggest a function of p44/42 MAPK for adrenal growth and a role of p44/42 MAPK for the integration of different endocrine stimuli.

P-64 Decreased p44/42 MAPK phosphorylation in gender- or hormone-related but not during age-related adrenal gland growth in mice

Postnatal growth of the mouse adrenal gland shows a characteristic gender-dependent pattern, resulting in an almost two-fold higher adrenal weight in 11-week-old female versus male mice. We demonstrated that the higher weight of the adrenal glands in female mice is due to a significantly (p<0.05) increased growth rate in female mice and a shorter growth phase of the adrenal glands in male mice (p<0.05). To address the signaling mechanisms underlying these differential growth patterns, we evaluated the phosphorylation levels of p44/42 and p38 MAPK. In female mice, age dependent reductions of p38 MAPK phosphorylation were found between week 3 and week 9 (47% reduction; p<0.05). At the age of 11 weeks the p38 MAPK phosphorylation level in female adrenal glands was about 60% lower than in the male counterparts (p<0.01). Similarly the phosphorylation level of p44/42 MAPK was 50% lower in female adrenal glands (p<0.001). Reduced activation of p44/42 MAPK was also observed after growth stimulation of the adrenal glands in male mice after ACTH treatment (-36%; p<0.001) or by expression of a growth hormone transgene (-34%; p<0.001), while p38 MAPK, JNK or PDK1 activation were unaffected. From our findings in three independent mouse models where partial deactivation of p44/42 MAPK was observed under conditions of elevated growth we suggest a function of p44/42 MAPK for adrenal growth and a role of p44/42 MAPK for the integration of different endocrine stimuli.

Induction of T 4 UDP-GT activity, serum thyroid stimulating hormone, and thyroid follicular cell proliferation in mice treated with microsomal enzyme inducers

The microsomal enzyme inducers phenobarbital (PB), pregnenolone-16α-carbonitrile (PCN), 3-methylcholanthrene (3MC), and Aroclor 1254 (PCB) are known to induce thyroxine (T 4) glucuronidation and reduce serum T 4 concentrations in rats. Also, microsomal enzyme inducers that increase serum TSH (i.e., PB and PCN) also increase thyroid follicular cell proliferation in rats. Little is known about the effects of these microsomal enzyme inducers on T 4 glucuronidation, serum thyroid hormone concentrations, serum TSH, and thyroid gland growth in mice. Therefore, we tested the hypothesis that microsomal enzyme inducers induce T 4 UDP-GT activity, resulting in reduced serum T 4 concentrations, as well as increased serum TSH and thyroid follicular cell proliferation in mice. B6C3F male mice were fed a control diet or a diet containing PB (600, 1200, 1800, or 2400 ppm), PCN (250, 500, 1000, or 2000 ppm), 3MC (62.5, 125, 250, or 500 ppm), or PCB (10, 30, 100, or 300 ppm) for 21 days. All four inducers increased liver weight and hepatic microsomal UDP-GT activity toward chloramphenicol, α-naphthol, and T 4. PB and PCB decreased serum total T 4, but PCN and 3MC did not. Serum thyroid stimulating hormone was markedly increased by PCN and 3MC treatments, and slightly increased by PB and PCB treatments. All four microsomal enzyme inducers dramatically increased thyroid follicular cell proliferation in mice. The findings suggest that PB, PCN, 3MC, and PCB disrupt thyroid hormone homeostasis in mice.

Inhibition by SMS 201-995 of normal mammary gland growth in mice.

Twice daily s.c. injection of 5 ng or 50 ng of SMS 201-995 between 25 and 55 days of age induced a significant retardation of normal mammary gland growth in C3H/He virgin mice, associated with the reduced plasma GH level. Meanwhile, plasma prolactin level and the pattern of estrous cycle were affected little by SMS treatments. The results indicate an involvement of GH in normal mammary gland growth in mice.

Synergistic effect of various hormones on experimental mammary gland growth in mice.

SummaryWhen 1 μg estradiol benzoate and 3 mg progesterone were administered to ovariectomized mice for 19 days, mammary gland development as measured by DNA was only 57.6% of that observed in mice on day 18 of pregnancy. Addition of thyroxine at level of 3 μg/100 g BW increased the DNA by 12.5%. Hydrocortisone acetate at a level of 100 μg/day increased DNA by 7% while the combination of the two hormones increased DNA by 17%. Lactogenic and growth hormones were ineffective as synergists. The highest level of DNA was obtained in ovari- and adrenalectomized animals given 100 μg Prednisone and varied EB and P, an increase to 11.67 mg/100 g BW or 19.9%.

Effect of anterior pituitary preparations on rat mammary gland growth.

SummaryUsing desoxyribosenucleic acid (DNA) as an index of mammary gland growth, crude and purified anterior pituitary extracts were tested for mammary gland growth promoting (mammogenic) effectiveness. Acetone dried AP powder and an initial extract of AP were shown to be effective in stimulating production of mammary gland DNA. Initial residue, Mammogen “A” and “C”, shown previously to produce mammary gland growth in mice, were found to be ineffective in rats. Fractions rich in lactogen and growth hormone were found to be minimally effective in stimulating mammary gland lobule-alveolar growth.

Effect of Recurring Pregnancy on Mammary Gland Growth in Mice

Summary It was shown by the increase of total desoxyribosenucleic acid (DNA) that mammary gland growth continues during the latter half of pregnancy. This observation was rather unexpected, since morphological study of lobule-alveolar growth can not distinguish between additional cell growth and the initiation of milk secretion. These data indicate for the first time that cell multiplication continues throughout pregnancy. The effect of recurring pregnancy on mammary gland growth was studied, employing albino mice bred successively without nursing periods. Maximum growth of the mammary glands was attained in triparous animals. A slight decline in total growth was observed in quadriparous animals. Their age at this time was estimated to be equivalent to the age of cows which begin to decline in yearly milk and fat yields. It was also confirmed that increased mammary gland growth in multiparous animals was more closely related to hormonal stimuli associated with recurring pregnancy and lactation than to increasing body weight. Primiparous mice after 3 mo. of involution had mammary glands containing DNA equivalent to mice pregnant for six days. No variation in average litter size was observed during four consecutive pregnancies.

Role of relaxin in stimulating mammary gland growth in mice.

Summary1) Using DNA as index of mammary gland lobule-alveolar growth in intact and castrate male mice, it was shown that daily injection of 0.75 μg estradiol benzoate and 2.5 GPU of relaxin for 10 days stimulated increases in DNA equal to that produced by the same level of estrogen and 0.75 mg progesterone. Therefore, relaxin no longer need be considered merely a synergist of estrogen and progesterone in mammary gland growth. 2) Estrogen and relaxin at above levels were without effect upon mammary alveolar growth in hypophysectomized mice. Relaxin, therefore, is not comparable to pituitary mammogen as a stimulator of mammary gland growth. 3) It is suggested estrogen and progesterone stimulate endogenous secretion of relaxin and relaxin, in turn, stimulates increased secretion of mammogen by the pituitary.