Serotonin: A Local Regulator in the Mammary Gland Epithelium

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is a very simple molecule that plays key roles in complex communication mechanisms within the animal body. In the mammary glands, serotonin biosynthesis and secretion are induced in response to dilation of the alveolar spaces. Since its discovery several years ago, mammary 5-HT has been demonstrated to perform two homeostatic functions. First, serotonin regulates lactation and initiates the transition into the earliest phases of involution. Second, serotonin is a local signal that induces parathyroid hormone-related peptide (PTHrP), which allows the mammary gland to drive the mobilization of calcium from the skeleton. These processes use different receptor types, 5-HT7 and 5-HT2, respectively. In this review, we provide synthetic perspectives on the fundamental processes of lactation homeostasis and the adaptation of calcium homeostasis for lactation. We analyze the role of the intrinsic serotonin system in the physiological regulation of the mammary glands. We also consider the importance of the mammary serotonin system in pathologies and therapies associated with lactation and breast cancer.

Serotonin Deficiency Rescues Lactation on Day 1 in Mice Fed a High Fat Diet

“…Notably, both HFD groups had smaller alveoli than their LFD counterparts, and Tph1 -/- dams had more alveoli than WT dams, regardless of diet. Serotonin can have a variety of effects on mammary gland alveolar cell proliferation and differentiation, dependent on both dose and timing of lactation [36]. Given the time sensitivity of this local regulator, further exploration of lactating mammary glands on day 1 is necessary to fully examine the role of serotonin in milk synthesis with respect to DOL and obesity.…”

An interpretive review of selective sweep studies in Bos taurus cattle populations: identification of unique and shared selection signals across breeds

“…For the Single-breed CSSs associated with dual-purpose breeds, the top 10 significant terms were mainly related to cell signaling pathways involving two important mitogen-activated protein kinases ( MAP2K2, MAPK3 ), which are linked to pathways involving receptors of serotonin and histamine (see Table 3 ). Whereas serotonin is a local regulator in the mammary gland that regulates lactation and initiates the transition into the earliest phases of the involution process related to the return of the mammary gland to morphologically near pre-pregnant state (Horseman and Collier, 2014 ), the histamine receptors may, in addition to their involvement in local immune responses, also show central effects on modulation of behavior related to the biological function of histamine as a neurotransmitter in the central nervous system (Schneider et al, 2014 ). The analysis of the dual-purpose-related Single-breed CSSs also revealed over-representation of genes involved in myometrial relaxation and contraction pathways, which could be related to the selection of females that are good dairy cows and can also give birth to calves with meat-production characteristics (e.g., large size).…”

The Type 7 Serotonin Receptor, 5-HT7, Is Essential in the Mammary Gland for Regulation of Mammary Epithelial Structure and Function

“…A critical cell physiological event in mammary epithelial homeostasis is the opening of tight junctions in response to 5-HT-mediated p38 MAPK signaling [ 2 , 15 , 16 , 20 ]. Because tight junctions are the only planar cell-cell junctions in the lactating mammary epithelium [ 28 , 29 ], failure of tight junction disruption in HT7KO glands is sufficient to explain the defects observed during milk stasis.…”