Similar to the stud on estrogen receptor decrease, this study shows that the saturated progesterone metabolite 5α-dihydroprogesterone (5α-DHP) is more effective than progesterone at inhibiting prolactin release from the
pituitary. Just as in the estrogen study, the effective doses of 5α-DHP were 2-3 times lower than the ones needed for progesterone and the most effective dose of 5α-DHP was a relatively low HED of 0.3mg/kg, which brought about a 70% decrease in prolactin release.
https://www.ncbi.nlm.nih.gov/pubmed/19215357
"...The purpose of this study was to examine whether the effect of different doses of progesterone on estrogen-induced prolactin release correlated with the effects of progesterone on estrogen receptor dynamics of the anterior pituitary demonstrated by Fuentes et al. (13). In our study, the 0.8 mg/kg body wt and 3.2 mg/kg body wt doses of progesterone inhibited estrogen-induced prolactin release (64% and 60% reduction) whereas the 2.0mg/kg body wt dose was ineffective (4% reduction)."
"...In view of the uniqueness of this observation it was important to confirm that two doses of the same steroid were active in bringing about a biological change while the intermediate dose was either ineffective or minimally effective. For this purpose we sought out another steroid 5a-dihydroprogesterone, which was related to progesterone and interacted with the progesterone receptor. It also was reported to bring about the selective release of follicle-stimulating hormone by Murphy and Mahesh (15). Progesterone is actively metabolized by both the hypothalamus and anterior pituitary to various metabolites, principally 5adihydroprogesterone (14). 5a-dihydroprogesterone has been shown to bind with high affinity to the progesterone receptor in a variety of tissues (21 -23). In this study 5a-dihydroprogesterone was found to inhibit estrogen-induced prolactin release similar to progesterone (Fig. 2)."
"...The effect of 5a-dihydroprogesterone upon estradiol-induced prolactin release was influenced by the dose used (Fig. 2). Similar to progesterone, Sa-dihydroprogesterone caused a decrease or no effect on pituitary nuclear estradiol receptors depending upon the dose used (24). A strong correlation was found between those doses which depleted pituitary-occupied nuclear estrogen receptors in the Fuentes et al. study (13) and those that inhibited estradiol-induced prolactin release in this study. In the study of Fuentes et al. (24), the 0.2 mg/kg body wt and 2.0 mg/kg body wt doses of 5α-dihydroprogesterone were more effective in reducing occupied pituitary estrogen receptor levels (54% and 74% reduction; P < 0.01 for both groups) as compared to the 0.8 mg/kg body wt dose (31% reduction) in which the reduction was not significant. In our study, the 0.4 mg/kg body wt and 2.0 mg/kg body wt doses of 5α-dihydroprogesterone inhibited estrogen-induced prolactin release (68% reduction for each), whereas the 0.8 mg/kg body wt dose was ineffective (17% reduction)."
"...Of considerable interest is the finding that 5α-dihydroprogesterone is twice as potent as progesterone with respect to its effect upon both the estrogen receptor depletion (24) and inhibition of estrogen-induced prolactin secretion (compare Fig. 1 vs Fig. 2). Murphy and Mahesh also reported that the 0.4 mg/kg body wt dose of 5α-dihydroprogesterone brought about selective release of follicle-stimulating hormone in ovariectomized estrogen-primed immature rats (15) and adult rats ovariectomized on the day of proestrus (19), while the 0.8 mg/kg body wt dose was ineffective. The higher potency of 5α-dihydroprogesterone compared to progesterone may suggest a critical role for 5α-dihydroprogesterone as an active mediator of progesterone action at the level of the anterior pituitary."
pituitary. Just as in the estrogen study, the effective doses of 5α-DHP were 2-3 times lower than the ones needed for progesterone and the most effective dose of 5α-DHP was a relatively low HED of 0.3mg/kg, which brought about a 70% decrease in prolactin release.
https://www.ncbi.nlm.nih.gov/pubmed/19215357
"...The purpose of this study was to examine whether the effect of different doses of progesterone on estrogen-induced prolactin release correlated with the effects of progesterone on estrogen receptor dynamics of the anterior pituitary demonstrated by Fuentes et al. (13). In our study, the 0.8 mg/kg body wt and 3.2 mg/kg body wt doses of progesterone inhibited estrogen-induced prolactin release (64% and 60% reduction) whereas the 2.0mg/kg body wt dose was ineffective (4% reduction)."
"...In view of the uniqueness of this observation it was important to confirm that two doses of the same steroid were active in bringing about a biological change while the intermediate dose was either ineffective or minimally effective. For this purpose we sought out another steroid 5a-dihydroprogesterone, which was related to progesterone and interacted with the progesterone receptor. It also was reported to bring about the selective release of follicle-stimulating hormone by Murphy and Mahesh (15). Progesterone is actively metabolized by both the hypothalamus and anterior pituitary to various metabolites, principally 5adihydroprogesterone (14). 5a-dihydroprogesterone has been shown to bind with high affinity to the progesterone receptor in a variety of tissues (21 -23). In this study 5a-dihydroprogesterone was found to inhibit estrogen-induced prolactin release similar to progesterone (Fig. 2)."
"...The effect of 5a-dihydroprogesterone upon estradiol-induced prolactin release was influenced by the dose used (Fig. 2). Similar to progesterone, Sa-dihydroprogesterone caused a decrease or no effect on pituitary nuclear estradiol receptors depending upon the dose used (24). A strong correlation was found between those doses which depleted pituitary-occupied nuclear estrogen receptors in the Fuentes et al. study (13) and those that inhibited estradiol-induced prolactin release in this study. In the study of Fuentes et al. (24), the 0.2 mg/kg body wt and 2.0 mg/kg body wt doses of 5α-dihydroprogesterone were more effective in reducing occupied pituitary estrogen receptor levels (54% and 74% reduction; P < 0.01 for both groups) as compared to the 0.8 mg/kg body wt dose (31% reduction) in which the reduction was not significant. In our study, the 0.4 mg/kg body wt and 2.0 mg/kg body wt doses of 5α-dihydroprogesterone inhibited estrogen-induced prolactin release (68% reduction for each), whereas the 0.8 mg/kg body wt dose was ineffective (17% reduction)."
"...Of considerable interest is the finding that 5α-dihydroprogesterone is twice as potent as progesterone with respect to its effect upon both the estrogen receptor depletion (24) and inhibition of estrogen-induced prolactin secretion (compare Fig. 1 vs Fig. 2). Murphy and Mahesh also reported that the 0.4 mg/kg body wt dose of 5α-dihydroprogesterone brought about selective release of follicle-stimulating hormone in ovariectomized estrogen-primed immature rats (15) and adult rats ovariectomized on the day of proestrus (19), while the 0.8 mg/kg body wt dose was ineffective. The higher potency of 5α-dihydroprogesterone compared to progesterone may suggest a critical role for 5α-dihydroprogesterone as an active mediator of progesterone action at the level of the anterior pituitary."