Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis.

The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq.

Lipid Droplet Fusion in Mammary Epithelial Cells is Regulated by Phosphatidylethanolamine Metabolism.

Mammary epithelial cells (MEC) secrete fat in the form of milk fat globules (MFG) which are found in milk in diverse sizes. MFG originate from intracellular lipid droplets, and the mechanism underlying their size regulation is still elusive. Two main mechanisms have been suggested to control lipid droplet size.

CLOCK regulates mammary epithelial cell growth and differentiation.

Circadian clocks influence virtually all physiological processes, including lactation. Here, we investigate the role of the CLOCK gene in regulation of mammary epithelial cell growth and differentiation. Comparison of mammary morphology in late-pregnant wild-type and ClockΔ19 mice, showed that gland development was negatively impacted by genetic loss of a functional timing system.

Regulation of lipid droplet size in mammary epithelial cells by remodeling of membrane lipid composition-a potential mechanism.

Milk fat globule size is determined by the size of its precursors-intracellular lipid droplets-and is tightly associated with its composition. We examined the relationship between phospholipid composition of mammary epithelial cells and the size of both intracellular and secreted milk fat globules. Primary culture of mammary epithelial cells was cultured in medium without free fatty acids (control) or with 0.

MiR-21 is under control of STAT5 but is dispensable for mammary development and lactation.

Development of mammary alveolar epithelium during pregnancy is controlled by prolactin, through the transcription factors STAT5A/B that activate specific sets of target genes. Here we asked whether some of STAT5's functions are mediated by microRNAs. The miR-21 promoter sequence contains a bona-fide STAT5 binding site and miR-21 levels increased in HC11 mammary cells upon prolactin treatment.

Effect of photoperiod and heat stress in the third trimester of gestation on milk production and circulating hormones in dairy goats.

The influence of photoperiod manipulation in the dry period was examined in dairy goats experiencing environmental heat stress. Multiparous Israeli Saanen goats were blocked at dry off (∼60 d prepartum) into 2 groups of 4 goats each based on body weight, previous milk production, and detected embryo number. Treatments consisted of long-day (16 h light:8 h dark) and short-day (8 h light:16 h dark) photoperiods (LDPP and SDPP, respectively).

Elongation and desaturation pathways in mammary gland epithelial cells are associated with modulation of fat and membrane composition.

The aim was to determine the relative role of each of the lactogenic hormones (insulin, prolactin and hydrocortisol) and their combinations in regulating elongation and desaturation of polyunsaturated fatty acids and subsequently on composition of cellular lipid compartments in mammary epithelia. Cultured cells of the mammary gland epithelial cell line HC11 were subjected to 48 h of hormonal treatment with different combinations of insulin, hydrocortisone and prolactin. Only the combination of all three hormones induced differentiation according to the marker β-casein gene expression.

Hyperinsulinemic clamp modulates milk fat globule lipid composition in goats.

We determined the effect of insulin on milk fatty acid (FA) and lipid composition in goats. Four dairy goats, 150 d in milk, were subjected to hyperinsulinemic clamp (treatment) or saline (control) infusion for 4d in a crossover design study. Composition and concentration of plasma and milk FA, triglycerides, phospholipids, sphingolipids, and cholesterol were determined.

Long-term effects of ad libitum whole milk prior to weaning and prepubertal protein supplementation on skeletal growth rate and first-lactation milk production.

Our objectives were to determine the effects of rapid growth rate during the preweaning period and prepubertal protein supplementation on long-term growth pattern and milk production during the first lactation. Forty-six Israeli Holstein heifer calves were fed either milk replacer (MR) or whole milk (WM) from 4 to 60 d age. Calves had free access to WM or MR for 30 min twice daily and free-choice water and starter mix for the entire day.

Mammary Fat Can Adjust Prolactin Effect on Mammary Epithelial Cells via Leptin and Estrogen.

Leptin, like estrogen, is one of the endo/paracrine factors, which are synthesized in and secreted from mature adipocytes. The roles of the mammary fat pad and mammary adipocytes in the initiation of lactation are not clear. In this study, we showed that combination of prolactin, leptin and estrogen elevated the expression of the milk protein beta-lactoglobulin.

Leptin up-regulates the lactogenic effect of prolactin in the bovine mammary gland in vitro.

The ability of leptin to up-regulate prolactin action in the mammary gland is well established. We examined the effect of leptin and prolactin on traits associated with lactation. Leptin and prolactin enhanced proliferation (thymidine incorporation) of the mammary gland cells, elevated the cells' proliferation in a dose-responsive manner, and synergized to elevate the expression of amino acid metabolism via a 90% increase in aminopeptidase N expression.

Increased serum leptin and insulin concentrations in canine hypothyroidism.

Serum concentrations of leptin and insulin were compared between gender-matched hypothyroid (n=25) and healthy (n=25) client-owned dogs within comparable age and body condition score (BCS) ranges. Fasted blood samples were collected from each dog and analysed for glucose, cholesterol, triglyceride, leptin and insulin concentrations. Leptin and insulin concentrations were significantly higher in the hypothyroid compared to normal dogs (P=0.

Heat production and retained energy in lactating cows held under hot summer conditions with evaporative cooling and fed two rations differing in roughage content and in vitro digestibility.

The objective of this study was to measure the effect of feeding two total mixed rations (TMRs), differing in their roughage content and in vitro dry matter (DM) digestibility, on the physiological response and energy balance of lactating cows. The partitioning of metabolizable energy intake (MEI) between heat production (HP) and retained energy (RE) of cows held under hot weather conditions and external evaporative cooling was measured. In all, 42 lactating cows were divided into two similar sub-groups, each of 21 animals, and were fed either a control (CON) ration containing 18% roughage neutral detergent fiber (NDF) or an experimental (EXP) TMR containing 12% roughage NDF and used soy hulls as partial wheat silage replacer.

Effect of photoperiod in the third trimester of gestation on milk production and circulating hormones in dairy goats.

Multiparous Israeli Saanen goats (n = 8) were blocked at dry off (approximately 45 d prepartum) into 2 treatments of 4 goats each based on body weight (BW), previous milk production, and the number of detected embryos in utero. Treatments consisted of long-day (16 h light:8 h dark) and short-day (8 h light:16 h dark) photoperiods at normothermic ambient temperature (22 degrees C, 72% relative humidity). All goats were returned to ambient photoperiod after kidding, milked twice daily, and milk yield was automatically recorded.

A high-fat diet has a tissue-specific effect on adiponectin and related enzyme expression.

Objective: This study was designed to test whether adiponectin plays a role in diet-induced obesity and insulin resistance and acts as a mediator to induce or inhibit specific metabolic pathways involved in lipid metabolism

Research Methods And Procedures: Forty C57BL/6J male mice were fed either a high-fat (HF) or control diet for 4 months, and adiponectin, its receptors, and enzyme expression in liver and muscle tissue were measured.

Results: Mice fed the HF diet exhibited significantly greater weight gain, abnormal oral glucose tolerance test curves, and elevated homeostasis model assessment of insulin resistance (5.3 +/- 0.

Prolactin affects leptin action in the bovine mammary gland via the mammary fat pad.

One of the roles of the endocrine system is to synchronize mammary function. Hormones, such as estrogen, progesterone, and prolactin act directly on the mammary gland. Metabolic hormones, such as GH, glucocorticoids, insulin, and leptin are responsible for coordinating the body's response to metabolic homeostasis.

Expression of relaxin receptor LRG7, canine relaxin, and relaxin-like factor in the pelvic diaphragm musculature of dogs with and without perineal hernia.

Objectives: To compare the expression of canine relaxin, relaxin-like factor (RLF), and relaxin receptors within the muscles of the pelvic diaphragm of dogs with perineal hernia (PH) and clinically normal dogs.

Study Design: In vivo comparative study.

Animals: Fifteen client-owned intact male dogs with PH were studied.

Aminopeptidase N gene expression and abundance in caprine mammary gland is influenced by circulating plasma peptide.

This study examined the localization and the effect of circulating peptides on the expression of aminopeptidase N (EC 3.4.11.

Role of xanthine oxidase, lactoperoxidase, and NO in the innate immune system of mammary secretion during active involution in dairy cows: manipulation with casein hydrolyzates.

The aims of this study were to test whether xanthine oxidase, lactoperoxidase, and NO are components of the innate immune system of mammary secretion during active involution in dairy cows, and whether the innate immune system is activated by casein hydrolysates. Our laboratory has shown recently that infusion of CNH into mammary glands induced involution and was associated with earlier increases in the concentrations of components of the innate immune system. Intact casein is inactive and served as control.

Effect of nursing management and skeletal size at weaning on puberty, skeletal growth rate, and milk production during first lactation of dairy heifers.

Forty Israeli-Holstein 5-d-old calves were used to determine the effect of increasing calf body weight (BW) and skeletal size during the nursing period on age and skeletal size at puberty and on skeletal size and performance during first lactation. The calves were randomly allotted to 2 experimental groups as follows: milk replacer (MR) [calves were given 0.450 kg/d dry matter of milk replacer for the first 50 d of life] and milk-fed (MF) [calves had free access to milk in two 30-min meals/d].

Expression of albumin in nonhepatic tissues and its synthesis by the bovine mammary gland.

Albumin is a well-characterized product of the liver. In the present study, objectives were to determine if the albumin gene is also expressed in various nonhepatic tissues in the bovine; whether mammary gland epithelial cells synthesize albumin; and how its synthesis is affected by bovine mastitis. Albumin expression was monitored using reverse transcription-polymerase chain reaction.

Leptin affects prolactin action on milk protein and fat synthesis in the bovine mammary gland.

Leptin, a protein hormone produced and secreted predominantly by white adipose tissue, has a critical role in the regulation and coordination of energy metabolism. Identification of leptin in the milk of several mammals, including humans, led us to investigate its presence and regulatory effect in the cow mammary gland. The expression of leptin receptor in tissue culture of lactating mammary gland was augmented approximately 25 times by prolactin, but had no effect on virgin calf mammary tissue.

Changes in milk composition as affected by subclinical mastitis in sheep.

The mechanism of the effects of glandular-level subclinical mastitis in dairy sheep on milk yield and on its composition as expressed in curd yield was studied. Thirty-six Israeli-Assaf dairy sheep with one udder half infected with identified coagulase-negative staphylococci and the contralateral gland free of bacteria were chosen. The milk yield of the infected halves was significantly lower than that of the uninfected ones (0.

Infusions of casein hydrolyzates into the mammary gland disrupt tight junction integrity and induce involution in cows.

Milk stasis triggers local stimuli, which make the tight junctions leak and trigger involution. The aim of the study was to test the hypothesis that casein hydrolyzates compromise tight junction integrity and dry-off milk secretion in dairy cows. Six repeated doses of casein hydrolyzates after each milking during 3 d caused drastic changes in mammary secretion and composition, which were associated with irreversible cessation of milk secretion.