Little is known about the factors stimulating placental progesterone (P4) production at the time of the luteo-placental shift (6-8 weeks post-conception). To explore the regulatory mechanism, the effects of various steroids and peptides on the production of P4 by placental explants were studied. / In early placental explant culture P4 production was stimulated by 19-nortestosterone (19-NT), androstenedione (A-dione), 5$ alpha$-androstane-3$ alpha,$17$ beta$ diol (3$ alpha$-diol) and 5$ alpha$-androstane-3$ beta,$17$ beta$ diol (3$ beta$-diol). Of all the compounds tested, 19-NT had maximal effect. At term, P4 production was stimulated only by 3$ beta$-diol. 19-NT and A-dione were poorly aromatized in early placental explants compared to another androgen (Androst-5-ene-3$ beta,$17$ beta$ diol). / In accord with the above observations, placental levels of 19-NT and A-dione were higher in early gestation while the diols were higher in late gestation. / 19-NT stimulated P4 production in early placenta by effects on the conversion of P4 both from 25-hydroxycholesterol and from pregnenolone. The stimulatory influences of A-dione and 3$ alpha$-diol were mediated by increasing the P450scc activity. The specific increase of the conversion of P4 from pregnenolone accounted for the P4 stimulation observed by 3$ beta$- diol treatment of culture. / Cyloheximide (CH) treatment abolished the stimulatory influences of the aforementioned steroids on P4 production except for the initial phase of P4 stimulation by 19-NT, suggesting that all but the latter are dependent on protein synthesis. / P4 production was also stimulated and prolonged to 30 days in the presence of human maternal serum (HMS); a good correlation (r = 0.74, P $<$ 0.05) was seen between the histological appearance of the explants and P4 production. The stimulatory activity of HMS was heat labile, non-dialyzable and non-extractable into an organic solvent, suggesting that it is protein in nature. / In conclusion, this study suggests that 19-NT and A-dione are important for placental P4 production at the time of the luteo-placental shift. For in vitro study of placental hormonal regulation, HMS is a better nutrient supplement than fetal bovine serum.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.39328 |
| Date | January 1992 |
| Creators | Hasan, Jahanara Begum |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001277311, proquestno: NN74821, Theses scanned by UMI/ProQuest. |
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