Interesting study on Raloxifene and Tamoxifen on Prolactin levels

[Swifto]

Mol Cell Endocrinol. 2005 Jul 15;239(1-2):27-36.

Differential effects of estrogen receptor antagonists on pituitary lactotroph proliferation and prolactin release.

Kansra S, Yamagata S, Sneade L, Foster L, Ben-Jonathan N.

Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521, USA.

Anti-estrogens act by inhibiting estrogen receptor (ER) function. Unlike raloxifene and tamoxifen which exhibit both antagonist and agonist properties, ICI 182,*** (ICI) is considered a "pure" anti-estrogen devoid of any agonistic activities. Whereas there is ample information on the effects of anti-estrogens on the breast and uterus, little is known about their action on the pituitary, the estrogen-sensitive master endocrine gland. Our objectives were to: (1) compare the effects of ICI, tamoxifen and raloxifene on lactotroph proliferation in the absence of estrogen, (2) determine whether their action is mediated through the ER, and (3) compare their effects on prolactin (PRL) release. We are reporting that ICI is a potent inhibitor of lactotroph proliferation (both GH3 and MMQ cells) with maximal inhibition of 45-50% seen with 1nM. ICI is several orders of magnitude more potent than raloxifene while tamoxifen has no effect. Neither anti-estrogen affects T47D breast cancer cell proliferation. GH3 cell incubation with ICI for 1h only causes maximal suppression of cell proliferation, an effect which is reversed by co-incubation with estrogen. Such a short exposure to ICI is sufficient to cause rapid and persistent downregulation of ERalpha protein, whereas downregulation of ERbeta is significantly delayed; tamoxifen and raloxifene have no appreciable effects on ER(s) levels. The ability of ICI to inhibit GH3 cell proliferation is dependent upon ERalpha, since an ERalpha, but not ERbeta, specific agonist reverses the effect of ICI. PRL release is differentially regulated by the anti-estrogens. ICI at 0.1nM suppresses PRL release from GH3 cells by 80%, with a similar strong suppression also seen with 10nM raloxifene. However, tamoxifen at 0.01nM inhibits PRL release but has no effect at 10nM. Cell co-incubation with ICI and estradiol results in a four-fold increase in PRL release. Taken together, our study shows that ICI, in the absence of exogenous estrogens, inhibits lactotroph proliferation and PRL release by downregulating or inactivating ERalpha. The dissimilar responses of cell proliferation and PRL release to the anti-estrogens suggest that both processes are regulated by different mechanisms. These data highlight the importance of studying the effects of anti-estrogens in multiple systems.



Maybe some one can shed some more light on this.

It seems Ralox and Tamoxifen act differently on PRL release even though there so similar structurely?

It also seems Ralox has more of an inhibitive effect on the PRL than Tamox?

[Kratos]

Effects of raloxifene on circulating prolactin and estradiol levels in premenopausal women at high risk for developing breast cancer.Faupel-Badger JM, Prindiville SA, Venzon D, Vonderhaar BK, Zujewski JA, Eng-Wong J.
Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892-4254, USA. [email protected]

BACKGROUND: Prolactin is a peptide hormone necessary for normal breast development that may contribute to breast tumorigenesis. Estrogen is a significant positive regulator of prolactin synthesis; therefore, raloxifene, a selective estrogen receptor modulator under study as a breast cancer prevention agent, may modulate both estradiol and prolactin levels by inhibiting estradiol from binding to its receptor. METHODS: Premenopausal women at increased risk for invasive breast cancer participated in a pilot chemoprevention trial and were given 60 mg raloxifene daily for 24 months. Fasting serum samples collected at baseline and after 12 months on drug were used to measure circulating prolactin, estradiol, and sex hormone binding globulin (SHBG) levels. RESULTS: Of the 27 subjects who completed 12 months of raloxifene, 23 had paired prolactin samples, and 20 had paired estradiol and SHBG samples. Prolactin levels did not significantly change with raloxifene treatment, but SHBG levels increased (mean change = 7.3 nmol/L; P = 0.0001; 95% confidence interval, 3.9-10.7). Estradiol (mean change = 42 pg/mL; P = 0.048; 95% confidence interval, 1-84 pg/mL) levels were elevated when comparing 15 of the 20 women with paired estradiol measurements who also had both of these samples taken during the early follicular phase of the menstrual cycle. CONCLUSIONS: This report is the first to examine the long-term effects of raloxifene on prolactin, estradiol, and SHBG levels in premenopausal women who are also at increased risk for developing invasive breast cancer. Raloxifene had no significant effect on prolactin levels but did increase estradiol and SHBG measurements.

PMID: 16775175 [PubMed - indexed for MEDLINE]

[Kratos]

It's very interesting, but I think only academic at this point. Dopamine agonists are still the way to go when regulating prolactin.

[Swifto]

It's very interesting, but I think only academic at this point. Dopamine agonists are still the way to go when regulating prolactin.

Thanks Kratos. Havent seen that study you posted. Intresting.

[lemonada9]

Comparative effects of tamoxifen and bromocriptine on prolactin and pituitary weight in estradiol-treated male rats
Abstract
Male ACI rats were treated with estradiol to induce hyperprolactinemia and pituitary hypertrophy and hyperplasia. Animals received estradiol alone or with tamoxifen or bromocriptine for 4, 8, or 12 weeks. Estradiol treatment resulted in time-dependent increases in pituitary wet weight and serum prolactin concentrations. Tamoxifen completely blocked the increase in both variables; bromocriptine decreased but did not prevent time-dependent increases. Animals were also treated for 8 weeks with estradiol alone, followed by 4 weeks with estradiol and tamoxifen or bromocriptine. Neither compound reversed the hyperprolactinemia, although the pituitary wet weight of animals treated with bromocriptine was slightly but significantly reduced. These findings suggest that in this model if treatment is initiated simultaneously with estrogen stimulation, tamoxifen is more effective than bromocriptine at the doses studied; and, if therapy is initiated subsequent to the establishment of estrogen-induced hyperprolactinemia and pituitary hyperplasia, bromocriptine is more effective than tamoxifen at the doses studied.

Heres one that compares tamox to bromo.

Expression of prolactin receptor mRNA in oestrogen receptor positive breast cancers pre- and post-tamoxifen therapy.
CONCLUSION: Tamoxifen reduces expression of mRNA encoding the prolactin receptor in a sub-group of breast tumours and might provide the basis for a predictive test for tamoxifen therapy


Tamox might be helpful for prolactin induced gyno if started at same time as cycle. * kinda what ive gathered from these 2 studies


Testosterone replacement -induced hyperprolactinaemia: case report and review of the literature
Half of all men with prolactin (PRL)-producing macroadenomas present with hypogonadism, decreased libido and impotence, and therefore require testosterone replacement. However, very little is known about the effect of testosterone on prolactinomas. We report a case of an 18-year-old obese man who presented with hypogonadism and hyperprolactinaemia and underwent a transphenoidal hypophysectomy after a computer tomography scan showed the presence of a suprasellar macroadenoma. On separate occasions, we documented a rise in PRL when testosterone replacement was started and a fall in PRL when testosterone replacement was stopped (r=0.6090, P=0.0095). Furthermore, imaging studies suggested the possibility of tumour re-growth after testosterone therapy . We hypothesize that the exogenous testosterone was aromatized to oestradiol, which stimulated the release of PRL by the anterior pituitary. This was supported by the increase in oestradiol levels after testosterone replacement, although statistical significance was not achieved due to the availability of only a few data points. This case highlights the need to be aware of testosterone-replacement-induced hyperprolactinaemia, an under-recognized complication of androgen replacement in this setting. The use of aromatase inhibitors together with testosterone-replacement therapy or the use of non-aromatizable androgens might be indicated in such patients. Taken together, this report and previous studies show that dopamine agonists apparently do not suppress the hyperprolactinaemia induced by testosterone replacement.