Changes in PACAP Immunoreactivity in Human Milk and Presence of PAC1 Receptor in Mammary Gland during Lactation

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Breast milk is a complex biological fl uid that contains nutritional components and non-nutritive bioactive factors promoting survival and healthy development of the newborn. PACAP has important functions, as a bioactive factor, in reproductive and developmental processes. Shortly after its discovery, PACAP and its receptors were identifi ed in normal and cancerous mammary gland samples. The present review summarizes data obtained in breast milk during different periods of lactation by radioimmunoassay. Our group showed, for the fi rst time, that PACAP is present in the human milk at levels 5-to 20-fold higher than in the respective plasma samples. PACAP-like immunoreactivity (LI) is higher in colostrum compared to transitional and mature human milk samples. PACAP level seems stable until the 10th month of lactation and there after, a signifi cant increase can be observed between samples obtained in the interval 11th-17th months of breastfeeding. The presence of PACAP can also be confi rmed in milk and plasma samples from the most commonly used ruminant domestic animals (cow, sheep and goat), pasteurized cow milk and infant formula samples. Similarly to the human results, the concentration of PACAP in the milk whey is almost ten times higher than in the plasma of the respective animals, while pasteurized cow milk and infant formula samples contain PACAP-LI levels comparable to human milk samples. The exact function of PACAP in the milk is not known at the moment. We hypothesize that PACAP (1) is essential for the growth and development of the

Section: Abstract Pacap-like Immunoreactivity • Milk • Lactation • Masupporting

confidence: 88%

Section: Abstract Pacap-like Immunoreactivity • Milk • Lactation • Mamentioning

confidence: 99%

Section: Abstract Pacap-like Immunoreactivity • Milk • Lactation • Mamentioning

confidence: 99%

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Examination of PACAP During Lactation

Tamás

Vass

Helyes³

et al. 2016

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“…The N-terminal region of the polypeptide is evolutionary conserved and shows a high homology with that of VIP [ 5 ]. In the last decade, increasing amount of evidence has emerged regarding the important roles of PACAP in peripheral organs such as uterus [ 8 ], ovary [ 9 ], and teeth [ 10 ]; moreover, its presence has been proven in human milk [ 11 ]. Nonetheless, only sporadic data exist about its function in skeletal elements [ 12 -15 ].…”

Section: Pacap and Vipmentioning

confidence: 99%

Role of PACAP and VIP Signalling in Regulation of Chondrogenesis and Osteogenesis

Juhász

Tamás

Zákány

et al. 2016

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Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are multifunctional proteins that can regulate diverse physiological processes. These are also regarded as neurotrophic and antiinfl ammatory substances in the CNS, and PACAP is reported to prevent harmful effects of oxidative stress. In the last decade more and more data accumulated on the similar function of PACAP in various tissues, but its cartilage-and bone-related presence and functions have not been widely investigated yet. In this summary we plan to verify the presence and function of PACAP and VIP signalling tool kit during cartilage differentiation and bone formation. We give evidence about the protective function of PACAP in cartilage regeneration with oxidative or mechanically stress and also with the modulation of PACAP signalling in vitro in osteogenic cells. Our observations imply the therapeutic perspective that PACAP might be applicable as a natural agent exerting protecting effect during joint infl ammation and/or may promote cartilage regeneration during degenerative diseases of articular cartilage.

“…The action of PACAP on prolactin synthesis and release is complex and influenced by several factors [27,28]. The high concentrations of PACAP in the milk suggest that the peptide plays a role in the development of the newborn [29][30][31]. Equally possible function of PACAP in the milk is a local regulatory action of milk production and/or mammary gland development [32,33].…”

Section: Introductionmentioning

confidence: 99%

Occurrence and Functions of PACAP in the Placenta

Horváth

Németh

Brubel

et al. 2016

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Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide with a widespread distribution both in the nervous system and peripheral organs. The peptide is also present in the female gonadal system, indicating its role in reproductive functions. While a lot of data are known on PACAP-induced effects in oogenesis and in the regulation of gonadotropin secretion at pituitary level, its placental effects are somewhat neglected in spite of the documented implantation deficit in mice lacking endogenous PACAP. The aim of the present review is to give a brief summary on the occurrence and actions of PACAP and its receptors in the placenta. Radioimmunoassay (RIA) measurements revealed increased serum PACAP levels during the third trimester and several changes in placental PACAP content in obstetrical pathological conditions, further supporting the function of PACAP during pregnancy. Both the peptide and its receptors have been shown in different parts of the placenta and the umbilical cord. PACAP influences blood vessel and smooth muscle contractility of the uteroplacental unit and is involved in regulation of local hormone secretion. The effects of PACAP on trophoblast cells have been mainly studied in vitro. Effects of PACAP on cell survival, angiogenesis and invasion/proliferation have been described in different trophoblast cell lines. PACAP increases proliferation and decreases invasion in proliferative extravillous trophoblast cells, but not in primary trophoblast cells, where PACAP decreased the secretion of various angiogenic markers. PACAP pretreatment enhances survival of non-tumorous primary trophoblast cells exposed to oxidative stress, but it does not influence the cell death-inducing effects of methotrexate in proliferative extravillous cytotrophoblast cells. Interestingly, PACAP has pro-apoptotic effect in choriocarcinoma cells suggesting that the effect of PACAP depends on the type of trophoblast cells. These data strongly support that PACAP plays a role in normal and pathological pregnancies and our review provides an overview of currently available experimental data worth to be further investigated to elucidate the exact role of this peptide in the placenta. Abstract Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide with a widespread distribution both in the nervous system and peripheral organs. The peptide is also present in the female gonadal system, indicating its role in reproductive functions. While a lot of data are known on PACAP-induced effects in oogenesis and in the regulation of gonadotropin secretion at pituitary level, its placental effects are somewhat neglected in spite of the documented implantation deficit in mice lacking endogenous PACAP. The aim of the present review is to give a brief summary on the occurrence and actions of PACAP and its receptors in the placenta. Radioimmunoassay (RIA) measurements revealed increased serum PACAP levels during the third trimester and several changes in placental PACAP conten...