[Lotus]

In this study treatment with P+PRL (progesterone + prolactin) initiated a synergistic response of 400 fold higher with the combination. When E (estrogen) was co- administered with (P + PRL) it suppressed the effect of P+ PRL. 

Seen here:
Estradiol Represses Prolactin-Induced Expression of Na+/Taurocholate Cotransporting Polypeptide in Liver Cells through Estrogen Receptor-α and Signal Transducers and Activators of Transcription 5a
http://press.endocrine.org/doi/10.1210/en.2003-0752?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&


My takeaway from the study is trying a combo PC (progesterone cream) with a MSM cream...which promotes a PRL pathway known as STAT5. I'd like to point (however) that the mouse mammary glands are very similar in structure and function to human mammary (attached study below). Anyways...the STAT5 family of proteins is pretty incredible...I wrote about it many times....MSM promotes this pathway. 

Prolactin induces SHP-2 association with Stat5, nuclear translocation, and binding to the beta-casein gene promoter in mammary cells.
Chughtai N1, Schimchowitsch S, Lebrun JJ, Ali S.
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Abstract
The Src homology 2 (SH2) domain containing protein-tyrosine phosphatase SHP-2 contributes to prolactin receptor (PRLR) signal transduction to beta-casein gene promoter activation. We report for the first time that SHP-2 physically associates with the signal transducer and activator of transcription-5a (Stat5a), an important mediator of PRLR signaling to milk protein gene activation, in the mouse mammary HC11 and the human breast cancer T47D cells when stimulated with prolactin (PRL) and human growth hormone, respectively. In addition, overexpression studies indicate that the carboxyl-terminal SH2 domain of SHP-2 is required to maintain tyrosine phosphorylation of Stat5 and its interaction with SHP-2. Furthermore, we demonstrate by nuclear co-immunoprecipitation and indirect immunofluorescence studies that PRL stimulation of mammary cells leads to the nuclear translocation of SHP-2 as a complex with Stat5a. This process was found to involve the catalytic activity of the phosphatase. Finally, using the Stat5 GAS (gamma-activated sequence) element of the beta-casein gene promoter in electrophoretic mobility shift assays, we demonstrate that PRL induces the SHP-2-Stat5a complex to bind to DNA. The presence of the phosphatase in the protein-bound DNA complex was verified by using polyclonal antisera to SHP-2. Our studies indicate a tight physical and functional interaction between SHP2 and Stat5 required for regulation and perpetuation of PRL-mediated signaling in mammary cells and suggest a potential role for SHP-2 in the nucleus.



Mammary gland development—It’s not just about estrogen1 

Further evidence for convergence between the effects of P and PRL comes from various readouts of the response by MEC to this combination of hormones. In one approach, we administered all possible combinations of E, P, and PRL to sexually mature OVX mice and measured cellular proliferation 5 d later (Hovey et al., 2001). As expected, E alone increased MEC proliferation, whereas P or PRL alone had no effect. Consistent with their cooperative effect, treatment with P+PRL initiated a synergistic response such that cell division was 400- fold higher following treatment with this combination. Interestingly, when E was co- administered, it suppressed the effect of P+PRL, perhaps further highlighting an ability of P and PRL to function in-dependent of E. At the same time, there was proliferation in the adjacent MG stroma, although it remains unclear whether this response preceded or followed that in the epithelium. The synergistic response to P and PRL was also evident at the intracellular level through increased phosphorylation of the IR substrates 1 and 2 (Lee et al., 2003). Others have implicated additional local consequences that likely mediate the combined effects of P and PRL (Lee and Ormandy, 2012). 
https://www.ncbi.nlm.nih.gov/pmc/article...752091.pdf


The comparative pathology of human and mouse mammary glands.
Cardiff RD1, Wellings SR.
Author information

Department of Pathology and The Center for Comparative Medicine, University of California, Davis 95616, USA. rdcardiff@ucdavis.edu
Abstract
The mouse has emerged as a primary animal model for human breast cancer because the mammary glands of the two species are very similar in structure and function. In this regard the TDLU and LA have similar morphology. The mouse, infected by MMTV, develops "spontaneous" tumors with specific but limited tumor phenotypes. The advent of genetic manipulation has created transgenic mice that develop hyperplasias and tumors morphologically and cytochemically comparable to lesions in humans. Even experienced pathologists have difficulty distinguishing between lesions from the two species, and the morphological similarities support the utility of the mouse model in understanding human breast cancer. In this essay we review our experience with the histopathology of human and mouse mammary disease by comparing the normal gland with hyperplastic, dysplastic and neoplastic lesions of traditional and transgenic origin.