scholarly journals Suppression of lactation and acceleration of involution in the bovine mammary gland by a selective serotonin reuptake inhibitor

2011 ◽  
Vol 209 (1) ◽  
pp. 45-54 ◽  
Author(s):  
L L Hernandez ◽  
J L Collier ◽  
A J Vomachka ◽  
R J Collier ◽  
N D Horseman

Serotonin (5-HT) is a homeostatic regulator of lactation. Selective 5-HT reuptake inhibitors (SSRI) are commonly prescribed pharmaceuticals that inhibit activity of the 5-HT reuptake transporter, increasing cellular exposure to 5-HT. Use of SSRIs has been shown to alter lactation performance in humans and 5-HT has been shown to reduce milk yield in cattle. However, it has not been determined how SSRI treatments affect the bovine mammary gland. We evaluated the effects of SSRI (fluoxetine (FLX)) administration on tight junctions (TJs) and milk protein gene expression in a lactogenic culture model, using primary bovine mammary epithelial cells (pBMEC). Additionally, we evaluated the effects of intramammary infusions of FLX and 5-hydroxytryptophan on milk production and TJ status in multiparous Holstein cows at dry-off. Treatment of pBMEC cultured on permeable membranes disrupted TJs, as measured by transepithelial resistance and immunostaining for zona occludens 1. Correspondingly, treatment of ‘3D’, collagen-embedded lactogenic cultures of pBMEC with FLX suppressed milk protein gene expression (α-lactalbumin and β-casein) in a concentration-dependent manner. Finally, intramammary treatment of Holstein cows with FLX resulted in an accelerated rate of milk decline. Additionally, TJ permeability increased in FLX-treated animals, as measured by plasma lactose and milk Na+ and K+ levels. Results of these experiments imply that SSRI administration accelerates the rate of mammary gland involution through disassembly of TJs and inhibition of milk protein gene expression in vitro and in vivo, leading to reduction of milk yield.

2004 ◽  
Vol 13 (Suppl. 1) ◽  
pp. 437-440 ◽  
Author(s):  
S. McCoard ◽  
N. Roy ◽  
B. Sinclair ◽  
M. Deighton ◽  
W. McNabb

1998 ◽  
Vol 18 (4) ◽  
pp. 1783-1792 ◽  
Author(s):  
Nathalie Cella ◽  
Bernd Groner ◽  
Nancy E. Hynes

ABSTRACT The lactogenic hormones, i.e., prolactin and glucocorticoids, act in concert to stimulate transcription factors responsible for hormone-dependent milk protein gene expression. In the mammary gland, prolactin activates Stat5a and Stat5b and glucocorticoids activate the glucocorticoid receptor (GR). Immunoprecipitation experiments revealed that in mammary cells, Stat5a, Stat5b, and the GR are physically associated in vivo. The association is not dependent on lactogenic hormone treatment and is evident at all stages of mammary gland development. Immunodepletion experiments indicated that a fraction of GR and Stat5 proteins are not associated, suggesting that there are different intracellular pools of these proteins. Lactogenic hormone treatment of HC11 mammary cells resulted in tyrosine phosphorylation of Stat5a and Stat5b, dimerization, and rapid nuclear translocation of both Stat5 proteins. Following hormone treatment, Stat5a-Stat5b heterodimers were detected by their coimmunoprecipitation. In addition, immunodepletion experiments followed by gel shift analyses revealed the presence of active Stat5a and Stat5b homodimers. In mammary cells, Stat5b homodimers are less abundant than Stat5a homodimers. Although the GR does not bind the Stat5 DNA binding site directly, it could be detected with the Stat5-DNA complex. These results suggest that glucocorticoids affect milk protein gene expression via association of the GR with Stat5. Thus, there is a functional coupling between Stat-dependent and nuclear hormone receptor-dependent gene transcription.


1982 ◽  
Vol 16 (2) ◽  
pp. 165-186 ◽  
Author(s):  
Pradman K. Qasba ◽  
Abhaya M. Dandekar ◽  
Toby M. Horn ◽  
Ilona Losonczy ◽  
Mary Siegel ◽  
...  

1982 ◽  
pp. 275-290
Author(s):  
Jeffrey M. Rosen ◽  
Andrew A. Hobbs ◽  
M.L. Johnson ◽  
John R. Rodgers ◽  
Li Y. Yu-Lee

2004 ◽  
Vol 71 (2) ◽  
pp. 135-140 ◽  
Author(s):  
Paul A Sheehy ◽  
James J Della-Vedova ◽  
Kevin R Nicholas ◽  
Peter C Wynn

A method for the collection of mammary biopsies developed previously was refined and used to study the endocrine regulation of bovine milk protein gene expression. Our surgical biopsy method used real-time ultrasound imaging and epidural analgesia to enable recovery of a sufficient quantity of mammary tissue from late-pregnant dairy cows for explant culture in vitro. The time of biopsy was critical for prolactin-dependent induction of milk protein gene expression in mammary explants, as only mammary tissue from cows nearing 30 d prepartum was hormone-responsive. This suggests that during the later stages of pregnancy a change in the responsiveness of milk protein gene expression to endocrine stimuli occurred in preparation for lactation. This may relate to the diminution of a putative population of undifferentiated cells that were still responsive to prolactin. Alternatively, the metabolic activity of the tissue had increased to the level whereby the response of the tissue was no longer assessable using this model in vitro.


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