Peripheral and ovarian vein plasma levels of 20α-dihydroprogesterone in women with normal menstrual cycles

Lucisano, A.; Dell'Acqua, S; Montemurro, A.; Rossetti, A.C.; Cinque, B.; Lafuenti, G; Arno, E.; Bompiani, A

doi:10.1016/0022-4731(78)90176-0

Cited by 7 publications

(5 citation statements)

References 15 publications

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“…In his early study Mikhail (1970) showed higher levels of 17-hydro¬ xyprogesterone in the venous blood draining the 'active' ovary compared to that secreted by the 'inactive' ovary; our results indicate that also this steroid is secreted by both ovaries. On the other hand, our data confirm those of several investiga¬ tors (Mikhail 1970;de Jong et al 1974;Calabresi et al 1976;Lucisano et al 1978) showing a higher progesterone level in the blood originating from the 'active' ovary compared to that from the 'inac¬ tive' one, but are at variance with the findings of Mikhail (1970), Calabresi et al (1976) and Lucisano et al (1978), who reported that the peripheral progesterone levels did not differ from those pre¬ sent in the venous blood from the 'inactive' ovary.…”

Section: Discussionsupporting

confidence: 86%

Ovarian steroid secretion in normally menstruating women II. The contribution of the corpus luteum

Aedo

Pedersen

et al. 1980

Acta Endocrinologica

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In 9 normally menstruating women undergoing surgical sterilization by tubal ligation the levels of 12 unconjugated steroids and 4 steroid sulphates were analyzed in the peripheral circulation and in the venous blood draining both ovaries before and after the surgical removal of a freshly formed corpus luteum. In addition, the peripheral levels of progesterone, 20\g=a\-dihydroprogesterone, 17-hydroxyprogesterone, oestradiol and oestrone were measured during 3 pre-operative and 3 post-operative days. The levels of pregnenolone, 17-hydroxypregnenolone, progesterone, 20\g=a\-dihydroprogesterone and cortisol were significantly higher in the venous blood draining the 'active' ovary (containing the corpus luteum) than in the blood draining the contralateral 'inactive' ovary. Furthermore, compared to the values found in the peripheral blood, the levels of pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone and oestradiol were significantly higher in the blood draining both ovaries, whereas 20\g=a\-dihydroprogesterone, oestrone and cortisol levels were significantly higher only in the blood draining the 'active' ovary.Enucleation of the corpus luteum resulted in the following changes: 1) It abolished the previous differences between steroid levels of the blood draining the two ovaries, with the exception of the 20\g=a\-dihydroprogesteronelevels, which remained elevated in the blood draining the ovary that previously contained the corpus luteum.2) It diminished the levels of progesterone, 17-hydroxyprogesterone, 20\g=a\-dihydroprogesterone, androstenedione, oestradiol and oestrone and increased those of cortisol and pregnenolone sulphate in the blood draining the ovary from which the corpus luteum had been removed.3) It decreased the peripheral levels of progesterone and oestradiol and increased those of pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenedione, cortisol and pregnenolone sulphate. 4) After the removal of the corpus luteum, the levels of progesterone, 17-hydroxyprogesterone, androstenedione, testosterone and oestradiol remained significantly elevated in the venous blood draining both ovaries when compared to their peripheral levels. 5) The peripheral levels of progesterone, 17-hydroxyprogesterone, oestradiol and oestrone dropped to very low early follicular phase values within 24 h following the removal of the corpus luteum. In contrast, the levels of 20\g=a\-dihydroprogesterone reached early follicular phase levels only on the 3rd post-operative day. It is concluded that the most important steroids secreted by the human corpus luteum are progesterone, 20\ g=a\ \ x=r eq-\ dihydroprogesterone, 17-hydroxyprogesterone, oestradiol and oestrone. Some pregnenolone, 17-hydroxypregnenolone and androstenedione may also be secreted by the corpus luteum. In addition, both ovaries secrete progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, oestradiol and probably also pregnenolone, 17-hydroxypregnenolone a...

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Section: Discussionsupporting

confidence: 86%

Ovarian steroid secretion in normally menstruating women II. The contribution of the corpus luteum

Aedo

Pedersen

et al. 1980

Acta Endocrinologica

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“…Indeed, measurements of P4 levels in the ovarian vein of fertile women showed concentrations similar to the maximal concentrations used in our studies. 7 The mechanism for this apparent partial resistance to P4 is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…The concentrations of E2 and P4 used in these studies were close to levels measured in the ovarian vein of premenopausal women. 7,8 We next examined the effect of gonadotropin hormones on thymidine incorporation in ML5 cells (Fig. 1B).…”

Section: Effects Of Reproductive Hormones On Dna Synthesis In Culturedmentioning

confidence: 99%

Effect of Reproductive Hormones on Ovarian Epithelial Tumors: I. Effect

Zhou

Luo

Schönthal

et al. 2002

Cancer Biology & Therapy

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We examined the effects of the 4 major female reproductive hormones, estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH), and luteinizing hormone (LH) on thymidine incorporation in benign and malignant ovarian epithelial tumors cultured in vitro. Treatment of these tumors with E2, FSH and LH resulted in increased thymidine incorporation while treatment with P4 inhibited growth as well as thymidine incorporation. The inhibitory effect of progesterone could not be reproduced by treating the cells with ligands for other steroid hormone receptors known to interact with P4 such as the mineralocorticoid and glucocorticoid receptors. All cells lines expressed at least the PR-A isoform of the progesterone receptor. ORG2058, R5020, RU486, and ZK98299 acted as progesterone receptor agonists with regard to their effect on thymidine incorporation. P4 down-regulated cyclin B1 expression and cdk1 activity and up-regulated the p21 and p27 proteins. Expression of a reporter gene downstream to an AP-1 responsive element in a plasmid construct transfected into ovarian epithelial tumor cells was induced by P4 and inhibited by RU486. We conclude that P4 inhibits cell cycle activity in ovarian epithelial tumors, in part via down-regulation of the cdk1/cyclin B complex. This inhibitory effect may have therapeutic utility against ovarian epithelial tumors.

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“…However, because the ovary is a producer of P4 [16,51,52], cells within and even surrounding this organ are undoubtedly exposed to concentrations of this hormone that are orders of magnitude higher than circulating levels. Indeed, measurements of P4 levels in the ovarian vein of fertile women showed concentrations in the range of what was used in our study [53]. Therefore, it is conceivable that our in vitro observations might represent mechanisms that contribute to the protective effect of P4 against the development of ovarian epithelial tumors.…”

Section: Discussionmentioning

confidence: 67%

Suppression of the transformed phenotype and induction of differentiation‐like characteristics in cultured ovarian tumor cells by chronic treatment with progesterone

Blumenthal

Kardosh

Dubeau

et al. 2003

Molecular Carcinogenesis

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Epidemiological evidence suggests that elevated levels of the pregnancy hormone progesterone might play a role in the reduced risk of women to develop ovarian cancer. In vitro studies have supported this hypothesis by demonstrating negative effects of this hormone on the growth and proliferation of cultured ovarian carcinoma cells. However, little is known about the underlying molecular processes and how progesterone might decrease the risk for ovarian tumors. Therefore, we investigated the effects of chronic hormone treatment on the cell-cycle and transformed phenotype of ovarian carcinoma cell lines in vitro. We found that long-term treatment of these cells with progesterone caused a concomitant reduction of cyclin-dependent kinase (CDK) activity. In parallel, these cells lost their transformed phenotype as indicated by the acquisition of contact inhibition and the loss of anchorage-independence, as well as the reduced expression of tumor markers such as heat shock protein (HSP) 72 and carcinoma antigen (CA) 125. In addition, progesterone-treated cells exhibited characteristics that resembled a more differentiated phenotype. Taken together, our data indicated that progesterone was able to suppress the transformed phenotype of ovarian tumor cells. This observation could serve to explain progesterone's alleged protective effect in ovarian carcinogenesis.

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Peripheral and ovarian vein plasma levels of 20α-dihydroprogesterone in women with normal menstrual cycles

Cited by 7 publications

References 15 publications

Ovarian steroid secretion in normally menstruating women II. The contribution of the corpus luteum

Ovarian steroid secretion in normally menstruating women II. The contribution of the corpus luteum

Effect of Reproductive Hormones on Ovarian Epithelial Tumors: I. Effect

Suppression of the transformed phenotype and induction of differentiation‐like characteristics in cultured ovarian tumor cells by chronic treatment with progesterone

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