Cyclic changes in the mammary gland of cynomolgus macaques.
OBJECTIVE
To evaluate the influence of hormonal changes during the menstrual cycle on the mammary gland of female cynomolgus monkeys.


METHODS
Paired breast biopsy samples were obtained during the follicular and luteal phases of the cycle. Cycle characteristics were assessed by vaginal bleeding, serum hormones, vaginal cytology, and uterine ultrasound. The mammary gland was assessed by histology and immunohistochemistry for Ki67, estrogen receptors (ER) alpha and beta, progesterone receptors (PR), and cleaved caspase 3 (CPP32).


METHODS
Nonhuman primate study in an academic research environment.


METHODS
Fifty-two adult, female, feral cynomolgus macaques (Macaca fascicularis), aged 8 to 20 years, obtained from the breeding colony of the Institut Pertanian Bogor (Bogor, Indonesia).


METHODS
None


METHODS
Breast histomorphometry, immunohistochemical detection of Ki67, ERs, PR, and CPP32 in breast epithelial cells, and correlation with serum estradiol and progesterone.


RESULTS
Serum hormones, vaginal cytology and bleeding patterns were indicative of cycle stage. For lobules, Ki67 expression was higher in the follicular than in the luteal phase. In ducts, Ki67 expression was higher in the luteal than in the follicular phase. Estrogen receptors did not change across the cycle, but ER beta was more abundant. Ductal PR decreased in the luteal phase. Lobular CPP32 was higher during the luteal phase. Correlations of serum estradiol to outcomes varied by cycle stage.


CONCLUSIONS
These data indicate important regulatory differences in the balance of proliferation and apoptosis in epithelial subpopulations within the breast across the menstrual cycle, indicating different regulatory roles for ER alpha and beta.
The Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1040, USA.
Petra
P
Stute
Charles E
CE
Wood
Jay R
JR
Kaplan
J Mark
JM
Cline
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D005498:Follicular Phase / Q000097:blood; D019394:Ki-67 Antigen / Q000378:metabolism; D008183:Luteal Phase / Q000097:blood; D008252:Macaca fascicularis / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D008597:Menstrual Cycle / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D011374:Progesterone / Q000097:blood; D011980:Receptors, Progesterone / Q000378:metabolism
D015415:Biomarkers; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019394:Ki-67 Antigen; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; D053148:Caspase 3; D020169:Caspases