Doubt the impact of pioglitazone on NF-κB is relevant for breast development. ESTRADIOL ITSELF suppresses NF-κB.
https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr2255 Estrogen regulation of apoptosis: how can one hormone stimulate and inhibit? "Several studies have shown that E2 can inhibit the activity of NF-κB and thereby increase apoptosis. For example, Osipo and colleagues [35] reported that, in tamoxifen-resistant MCF-7 tumors, E2 treatment almost completely down-regulated the level of the NF-κB p65 subunit protein, which correlated with the anti-proliferative and pro-apoptotic effects of E2 in this model system".
The closest thing I found: rosiglitazone inhibits estrogen-independent breast growth induced by conjugated linoleic acid which is associated with metabolic syndrome.
"Lifetime breast cancer risk reflects an unresolved combination of early life factors including diet, body mass index, metabolic syndrome, obesity, and age at first menses. In parallel, the onset of allometric growth by the mammary glands around puberty is widely held to be estrogen (E)-dependent. Here we report that several physiological changes associated with metabolic syndrome in response to a diet supplemented with the trans-10, cis-12 isomer of conjugated linoleic acid lead to ovary-independent allometric growth of the mammary ducts. The E-independence of this diet-induced growth was highlighted by the fact that it occurred both in male mice and with pharmacological inhibition of either E receptor function or E biosynthesis. Reversal of the metabolic phenotype with the peroxisome proliferator-activated receptor-γ agonist rosiglitazone abrogated diet-induced mammary growth. A role for hyperinsulinemia and increased insulin-like growth factor-I receptor (IGF-IR) expression during mammary growth induced by the trans-10, cis-12 isomer of conjugated linoleic acid was confirmed by its reversal upon pharmacological inhibition of IGF-IR function. Diet-stimulated ductal growth also increased mammary tumorigenesis in ovariectomized polyomavirus middle T-antigen mice. Our data demonstrate that diet-induced metabolic dysregulation, independently of ovarian function, stimulates allometric growth within the mammary glands via an IGF-IR-dependent mechanism".
Breasts are mainly fat so it would be best to find studies about it. Pioglitazone stimulates creation of new fat cells in gluteofemoral depot but not abdominal visceral or even abdominal subcutaneous (which despite being subcutaneous is detrimental for health unlike gluteofemoral), depending on the study, reduces already existing abdominal fat. Interestingly, it increases pericardial fat which is visceral, but "this increase in pericardial fat volume did not negatively affect myocardial function after 24 wk", so it's not just lower body fat.
Thanks for taking the time to write your comment, am quite busy with irl stuff right now so haven't been able to read it yet but will get back to you over the coming days :)
Doubt the impact of pioglitazone on NF-κB is relevant for breast development. ESTRADIOL ITSELF suppresses NF-κB.
https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr2255 Estrogen regulation of apoptosis: how can one hormone stimulate and inhibit? "Several studies have shown that E2 can inhibit the activity of NF-κB and thereby increase apoptosis. For example, Osipo and colleagues [35] reported that, in tamoxifen-resistant MCF-7 tumors, E2 treatment almost completely down-regulated the level of the NF-κB p65 subunit protein, which correlated with the anti-proliferative and pro-apoptotic effects of E2 in this model system".
https://dspace.library.uu.nl/handle/1874/8772 Inhibition of NF-κB transcriptional activity by the estrogen receptor - Insights into the molecular mechanism
The closest thing I found: rosiglitazone inhibits estrogen-independent breast growth induced by conjugated linoleic acid which is associated with metabolic syndrome.
https://www.pnas.org/doi/full/10.1073/pnas.1210527109 (Diet-induced metabolic change induces estrogen-independent allometric mammary growth)
"Lifetime breast cancer risk reflects an unresolved combination of early life factors including diet, body mass index, metabolic syndrome, obesity, and age at first menses. In parallel, the onset of allometric growth by the mammary glands around puberty is widely held to be estrogen (E)-dependent. Here we report that several physiological changes associated with metabolic syndrome in response to a diet supplemented with the trans-10, cis-12 isomer of conjugated linoleic acid lead to ovary-independent allometric growth of the mammary ducts. The E-independence of this diet-induced growth was highlighted by the fact that it occurred both in male mice and with pharmacological inhibition of either E receptor function or E biosynthesis. Reversal of the metabolic phenotype with the peroxisome proliferator-activated receptor-γ agonist rosiglitazone abrogated diet-induced mammary growth. A role for hyperinsulinemia and increased insulin-like growth factor-I receptor (IGF-IR) expression during mammary growth induced by the trans-10, cis-12 isomer of conjugated linoleic acid was confirmed by its reversal upon pharmacological inhibition of IGF-IR function. Diet-stimulated ductal growth also increased mammary tumorigenesis in ovariectomized polyomavirus middle T-antigen mice. Our data demonstrate that diet-induced metabolic dysregulation, independently of ovarian function, stimulates allometric growth within the mammary glands via an IGF-IR-dependent mechanism".
Breasts are mainly fat so it would be best to find studies about it. Pioglitazone stimulates creation of new fat cells in gluteofemoral depot but not abdominal visceral or even abdominal subcutaneous (which despite being subcutaneous is detrimental for health unlike gluteofemoral), depending on the study, reduces already existing abdominal fat. Interestingly, it increases pericardial fat which is visceral, but "this increase in pericardial fat volume did not negatively affect myocardial function after 24 wk", so it's not just lower body fat.
Thanks for taking the time to write your comment, am quite busy with irl stuff right now so haven't been able to read it yet but will get back to you over the coming days :)