Progesterone-induced secretion of growth hormone ,insulin-like growth factor I and prolactin by human breast cancer explants

Abstract

The aim of the study was to evaluate the potential of human breast cancer tissue to secrete growth hormone (GH), insulin-like growth factor I (IGF-I) and prolactin in response to 10(-7) M progesterone stimulation. Explants were divided according to estrogen receptor (ER)/progesterone receptor (PR) phenotype (ER(-)PR(-); ER(+)PR(-); ER(+)PR(+); ER(-)PR(+)). Our results show distinct differences in cultured breast cancer tissue responses to progesterone stimulation with regard to secretion of proliferative agents such as GH, IGF-I and prolactin. All but ER(-)PR(-) breast cancer cell types responded in vitro to progesterone stimulation with an increase in local GH secretion, while in non-malignant tissue progesterone induced local GH secretion only in PR(+) cells. Moreover, only in PR(+) cells did progesterone stimulate local IGF-I and prolactin secretion, in both malignant and non-malignant tissue. This study provides evidence for the first time that in PR(+) breast cancer tissue, progesterone may increase GH, prolactin and IGF-I secretion in both malignant and surrounding non-malignant tissue. These hormones may act as local growth factors that stimulate the proliferation of mammary tumors.

Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination

“…For example, estradiol exerts its neuroprotective effects on the brain in synergy with IGF-I [156]. Reciprocal interactions between PROG, GH and IGF-I have also been reported in different experimental systems [157][158][159]. Thus, it is likely that the hormone and growth factor environment will influence the effectiveness of a steroidal treatment and vice versa.…”

Extrapituitary growth hormone

“…The expression of GH in the mammary gland is thought to be largely dependent upon progesterone [127,128], and mammary GH production is suppressed by ovariectomy [129] and by progesterone receptor antagonists [125,130]. It is thus of note that the progesterone receptor is colocalized with GH in the mammary gland [130].…”

Lack of synergy between estrogen and progesterone on local IGF-I, IGFBP-3 and IGFBP-2 secretion by both hormone-dependent and hormone-independent breast cancer explants in vitro. Effect of tamoxifen and mifepristone (RU 486)

“…They suggested that progestagens might be mitogenic in the breast tissue. We previously reported the stimulatory effect of progesterone on the activation of local hGH/IGF-I/IGF binding protein axis in breast tissue expressing progesterone receptors [5,6]. Moreover, we showed that the differences in secretion of hGH and IGF-I from breast tissue explants depended on the type of progestagens used and the steroid receptor phenotype of both malignant and adjacent non-malignant tissue [7].…”

“…Primary tumor explants were prepared according to Gregoraszczuk et al [5]. Briefly, explants from the malignant tissue and surrounding non-malignant tissue were trimmed into 0.5 cm 3 pieces, weighed and incubated in 2 ml of M199 phenol red free medium (Sigma, M3769) containing 5% of calf serum.…”