Seasonal fluctuations in the steady-state mRNA levels of suppressor of cytokine signaling-3 (SOCS-3) in the mammary gland of lactating and non-lactating ewes

doi:10.1016/j.smallrumres.2015.01.012

Small Ruminant Research

Volume 124, March 2015, Pages 101-104

https://doi.org/10.1016/j.smallrumres.2015.01.012 Get rights and content

Highlights

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SOCS-3 mRNA expression in ovine mammary gland is strongly dependent on the season.
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SOCS-3 mRNA expression in ovine mammary gland is dependent on the stage of lactation.
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The highest expression of SOCS-3 mRNA was noted in non-lactating sheep during SD.
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The lowest expression of SOCS-3 was observed in ewes on day 30 of lactation.

Abstract

Prolactin (PRL) is a hormone that plays a crucial role during pregnancy and lactation. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, which is an important pathway in signal transduction from PRL to target cells, can be modulated by various factors, including suppressor of cytokine signaling-3 (SOCS-3). PRL may increase and decrease SOCS-3 expression, and its actions are mostly dependent on additional factors such as the photoperiod. There is also evidence for a relationship between suckling and SOCS-3 expression in the mammary gland. The aim of this study was to examine the influence of seasonality and physiological status on SOCS-3 expression levels in ovine mammary glands. Mammary gland fragments were obtained from 18 Polish Longwool ewes, and the fine-needle aspiration biopsy technique was used on 4 groups of animals under specific physiological and photoperiodic conditions: non-lactating ewes during long days (LD; n = 6), ewes on day 30 (n = 6) or day 56 of lactation (n = 6) and non-lactating ewes during short days (SD; n = 6). SOCS-3 mRNA levels were measured by real-time PCR. The results of this study confirmed that SOCS-3 mRNA expression in sheep is dependent on the season and stage of lactation. The highest expression of the examined factors was noted in the mammary glands of non-lactating sheep during SD, and the lowest levels were observed in ewes on day 30 of lactation. The transcript levels observed in the tissues collected from non-lactating sheep during SD and LD were higher (74% and 41%, respectively) compared with the expression observed on day 30 of lactation. On day 56 of lactation, the SOCS-3 mRNA level was similar to that observed in the udders of non-lactating sheep during LD. These results indicate that SOCS-3 could play an integrating role between hormones and other factors that are involved in the physiological functions of the mammary gland.

Introduction

Prolactin (PRL) stimulates food intake during pregnancy and lactation by increasing the orexigenic drive and acting with estrogen and other factors. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is an important pathway for PRL signaling in target cells, and many previous studies have demonstrated that JAK/STAT pathway activation is a direct result of the binding of PRL to transmembrane receptors. The potency of PRL, however, may be decreased by cellular inhibitors such as the products of the suppressor of cytokine signaling (SOCS) genes particularly the SOCS-3 gene (Sutherland et al., 2007). SOCS-3 expression is influenced by a number of environmental and intrinsic factors, which include but are not limited to photoperiod (Wall et al., 2005) and nutritional status (Tups et al., 2004). PRL may increase or decrease SOCS-3 expression (Szczesna et al., 2011). However, there is a paucity of information regarding the changes in SOCS-3 expression in the mammary gland during different reproductive states in ewes. Therefore, the specific objective of this study was to evaluate the effect of photoperiod on SOCS-3 expression in the ovine mammary gland in lactating and non-lactating ewes.

Section snippets

Materials and methods

All of the animal-related procedures were approved by the Local Agricultural Animal Care and Use Committee of Krakow.

Results

In the present study, the highest SOCS-3 expression was observed in the mammary glands of the non-lactating sheep during the SD season, and the lowest SOCS-3 transcript levels were observed on day 30 of lactation (Fig. 1). SOCS-3 mRNA levels in the samples collected from the sheep on day 30 of lactation were lower (P < 0.05) than those of the non-lactating sheep mammary glands during the LD season. On day 56 of lactation (after weaning), SOCS-3 mRNA levels were increased (P < 0.01) compared with

Discussion

The present results confirmed that SOCS-3 mRNA expression in the ovine mammary gland is strongly dependent on the season as well as the occurrence and stage of lactation. To recapitulate, our results revealed that SOCS-3 mRNA expression was the lowest in April (LD) and after day 30 of lactation and the highest in November (SD) and at the end of lamb rearing. Previously, photoperiod-dependent fluctuations in SOCS-3 expression in sheep were only studied in the hypothalami and pituitary glands

Conclusion

The results of this study demonstrated that in sheep SOCS-3 expression levels in mammary glands are strongly influenced by the stage of lactation and seasonality. Further study are needed to indicate the role of SOCS-3 in maintaining homeostasis in the mammary gland by modulating proliferation and functional development during pregnancy and tissue remodeling during involution.

Conflict of interest statement

None declared.

Acknowledgements

This work was supported by a grant from the Polish National Science Center (NCN 2013/09/B/NZ4/01532). The authors thank Michal Nowakowski, MD, for his technical assistance.

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Cited by (3)

Phenomenon of leptin resistance in seasonal animals: The failure of leptin action in the brain
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Citation Excerpt :
SOCS3 may be a key factor in leptin-PRL crosstalk, which thereby participates in a potential mechanism through which the adjustment of energy homeostasis in response to the challenges of environmental (photoperiod) or physiological (pregnancy) changes is possible. Recently, we demonstrated in ovine mammary gland tissues that SOCS3 mRNA expression is dependent on the season and stage of lactation [79]. The highest expression of the examined factors was observed in the mammary glands of nonlactating sheep during SD, and the lowest levels were observed in ewes on day 30 of lactation (Fig. 7).
The core of the leptin resistance hypothesis promulgated several years ago to explain obesity as a result of environmental causes consists of 2 tenets: the extinction of leptin-induced intracellular signaling downstream of leptin binding to the long form of the neuronal receptor LTRb in the hypothalamus and the impedance to leptin entry imposed at the blood–brain barrier (BBB). A recent comprehensive investigation concluded that a central leptin insufficiency associated with obesity can be attributed to a decreased efficiency of BBB leptin transport and not to leptin insensitivity within the hypothalamus. Interestingly, anorectic leptin's effects are counteracted in some individuals by a natural resistance associated with hyperleptinemia, which is related to changes in hypothalamic sensitivity to leptin (eg, due to malnutrition, obesity, or seasonal variations due to day-length–dependent reproduction changes). In sheep, it has been observed that the hypothalamus is resistant to leptin in some periods, which is related to the adaptation of these animals to annual changes in energy supply and demand. However, a broad range of ambiguities exists regarding the implications that the intracellular signaling of signal transducer and activator of transcription-2/suppressor of cytokine signaling 3 (STAT2/SOCS3) imparts central leptin resistance. Furthermore, several plausible alternative possibilities have been proposed, such as compensatory functional and anatomic reorganizations in the appetite regulating network, rearrangements in the afferent hormonal feedback signaling involved in weight homeostasis, and modifications in leptin transport to the hypothalamus across the BBB. Taken together, these observations suggest that the contention that impaired intracellular signaling downstream of leptin entry into the appetite regulating network expedites environmentally induced obesity remains unsubstantiated and requires further evidence. Furthermore, pregnancy decreases hypothalamic sensitivity to leptin (or other unknown mechanisms), and lactation can also alter the appetite-suppressing central activity of leptin. The objective of this review was to offer an approach to understanding (1) how information regarding nutritional status is transmitted to and interpreted within the hypothalamus in animals, with special attention on seasonally breeding animals and (2) whether central leptin resistance and/or leptin insufficiency in the hypothalamus favors the development of obesity.
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View full text

Short communicationSeasonal fluctuations in the steady-state mRNA levels of suppressor of cytokine signaling-3 (SOCS-3) in the mammary gland of lactating and non-lactating ewes

Highlights

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Conclusion

Conflict of interest statement

Acknowledgements

Int. Dairy J.

Regul. Pept.

Int. Dairy J.

J. Dairy Sci.

Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3

Genes Dev.

Autocrine prolactin induced by the Pten–Akt pathway is required for lactation initiation and provides a direct link between the Akt and Stat5 pathways

Genes Dev.

Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor

Endocrinology

Socs2 and elf5 mediate prolactin-induced mammary gland development

Mol. Endocrinol.

Seasonal changes in the interactions between leptin, ghrelin and orexin in sheep

J. Anim. Sci.

SOCS1 deficiency results in accelerated mammary gland development and rescues lactation in prolactin receptor-deficient mice

Genes Dev.

Short communication
Seasonal fluctuations in the steady-state mRNA levels of suppressor of cytokine signaling-3 (SOCS-3) in the mammary gland of lactating and non-lactating ewes