Prolactine | EPFL Graph Search

La prolactine est une hormone peptidique sécrétée par les cellules lactotropes de la partie antérieure de l'hypophyse. Ses rôles sont multiples, elle intervient notamment dans la lactation, la reproduction, la croissance, l'immunité et le comportement. Structure La prolactine est une protéine constituée de 199 acides aminés chez l'être humain et de poids moléculaire . Sa structure 3D possède 3 ponts disulfures, formant 3 liaisons covalentes. Elle possède 48 % d'acides aminés en commun avec l'hormone de croissance. Physiologie Action Action chez les mammifères Action chez les amphibiens Chez les amphibiens, la prolactine joue un rôle dans la métamorphose (voir cycle de vie des amphibiens). Action chez les oiseaux Pour les oiseaux, la prolactine joue un rôle par exemple pour le lait de jabot et la plaque incubatrice. Régulation La PRF, Prolactin Releasing Factor, (ou PRH pour Prolactin Releasing Hormone)

Hormonal regulation of Stat5 in the mammary gland - from signaling to morphogenesis

Sergio Klinke

The mammary gland development is regulated by steroid and peptide hormones and occurs mainly after birth, compared to the majority of the other organs in the body. The principal hormones responsible for the breast development are the estrogen, the progesterone, the growth hormone, the epidermal growth factor and the prolactin. The latter one is of specific interest since it is required for further development of the gland through pregnancy and lactation. During pregnancy and lactation, alveolar structures develop and differentiate into secretory cells. The signal transducer and activator of transcription 5 (Stat5) is known to be the main effector of prolactin signaling during pregnancy, inducing alveologenesis and differentiation of epithelial cells into secretory cells. I investigated if Stat5 has a role before pregnancy. Protein expression as well as mRNA expression analysis of glands from ovariectomized mice which were artificially stimulated with ovarian hormones (estrogen and progesterone) and control vehicle showed evidences that Stat5 expression can be stimulated by these two hormones. Contrary to the role established until now for stat5 in the mammary gland, I found by fluorescence visualization of Stat5-null epithelium as well as whole mount staining of the same glands that Stat5 is required even before pregnancy since null epithelium showed highly reduced growth already in 3 weeks-old virgin mice. This may indicate a new role for this protein in cell proliferation or survival in early stages of mouse mammary development. Furthermore, transplantation experiment of Stat5-null epithelium into wild-type recipient mice showed that pregnancy state was not able to rescue the normal phenotype. This may be due to complete loss of these cells which happened during the 5 weeks left for the transplanted epithelium to expand the cleared fat pad. This discovery opens a new debate on Stat5 role in the mammary gland development.

2008

Activin Signalling in Human Melanoma Cells

Susanna Eveliina Kallioinen

Melanoma, the most fatal of all skin cancers, by unknown mechanisms overcomes the cytostatic effects of TGFβ, while maintaining the TGFβ signaling needed for its tumor promoting functions. Besides TGFβ, ectopic induction of the TGFβ family member Nodal has been reported in human melanoma to correlate with progression to metastatic growth. The same authors reported that a Smad2 morpholino antisense oligonucleotide delays Nodal-induced tumor growth of the aggressive melanoma cell line C8161 in xenograft assays. To investigate the underlying molecular mechanism, we compared C8161 melanoma cells with isogenic poorly metastatic C81-61 cells reportedly lacking Nodal expression. Unexpectedly, reverse transcription PCR, Western blot analysis using specific antibodies, and activity assays revealed that metastatic C8161 cells and many other human melanoma cell lines and tumors do not express Nodal, but frequently upregulate the related ligand Activin A. However, siRNA knockdown of Activin A did not reduce invasiveness of C8161 cells in matrigel, nor did the overexpression of Activin A in C81-61 cells increase it. The activity of Smad2,3 signaling was evaluated in the melanoma cell lines by a seriesWestern blot and reporter assays. The Smad signaling pathway was found to be attenuated in both C8161 and C81-61 cell lines, as only a small fraction of total Smad2,3 was detected in the nuclear fraction of the melanoma cells. In addition, little Smad3 signaling activity was observed by a Smad3-dependent luciferase reporter. To evaluate paracrine effects, human melanoma cells that do or do not express exogenous Activin A or Nodal were xenografted into nude mice. Neither Activin A nor Nodal enhanced metastatic growth in this assay. Inhibition of Activin A did also not alter metastasis formation. However, in the presence of the human fragment crytallisable region (Fc), Activin A seems to enhanced metastatic growth. Further studies are required to confirm these results, and to find the mechanism by which Activin A enhances metastatic potential.

EPFL2012

Prolactin controls mammary gland development via direct and indirect mechanisms

Cathrin Brisken

The inactivation of the prolactin receptor gene by homologous recombination has made it possible to investigate the role of prolactin signaling in mammary gland development without resort to ablative surgery of the endocrine glands. In knockout mice lacking the prolactin receptor, mammary development is normal up to puberty. Subsequently, the ducts branch less frequently than those of wild-type animals. While terminal end buds differentiate to alveolar buds in wild-type females by the end of puberty, in knockout females terminal end bud-like structures persist at the ductal ends. To distinguish between the developmental defects that are intrinsic to the epithelium and those that result from systemic endocrine alterations in prolactin receptor knockout mice, mammary epithelium from prolactin receptor knockouts was transplanted into mammary fat pads of wild-type mice. In virgin mice, the knockout epithelial transplants developed normally at puberty, indicating an indirect effect of prolactin on ductal development. Prolactin receptor knockout females are infertile due to multiple reproductive defects, but epithelial transplants allowed us to assess the extent to which the absence of prolactin receptor is limiting, under systemic conditions that allow full mammary gland development. During pregnancy, the prolactin receptor knockout transplants showed normal side branching and the formation of alveolar buds, but no lobuloalveolar development. Thus, prolactin affects mammary morphogenesis in two different ways: it controls ductal side branching and terminal end bud regression in virgin animals via indirect mechanisms, but acts directly on the mammary epithelium to produce lobuloalveolar development during pregnancy.

1999