The synthesis and metabolism of progesterone in the human and bovine ovary

Sweat, Max L.; Berliner, David L.; Bryson, Melvin J.; Nabors, Charles J.; Haskell, Jack G.; Holmstrom, E.G.

doi:10.1016/0006-3002(60)91353-6

Cited by 60 publications

(7 citation statements)

References 21 publications

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“…Previous studies with a human corpus luteum of the menstrua] cycle in vitro revealed the formation of radioactive progesterone and 20a-hydroxy-A 4 -pregnen-20-one from radioactive acetate (12). Other studies with radioactive steroid substrates in vitro have shown the over-all biosynthetic process in the human corpus luteum to proceed along the pathway: pregnenolone -^progesterone (->20a-hydroxy-A 4 -pregnen-20-one) -> 17-hydroxyprogesterone -> androstenedione -> estradiol-17/3and estrone (12)(13)(14)(15). Indications of a similar pathway have been reported for the follicle of the human ovary (16).…”

Section: Discussionmentioning

confidence: 77%

Steroid Hormone Formation in the Human Ovary: I. Identification of Steroids Formedin Vitrofrom Acetate-1-¹⁴C in the Corpus Luteum

Hammerstein

Rice

Savard

1964

The Journal of Clinical Endocrinology & Metabolism

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Slices of 6 human corpora lutea of the menstrual cycle and ectopic pregnancy were incubated in vitro in the presence of acetate-l-14 C. By means of carrier dilution and stringent purification measures, the biosynthesis of 7 radioactive steroids has been demonstrated in the 2 types of corpora lutea. These steroids include progesterone, 20a-hydroxy-A 4 -pregnen-3-one, 17-hydroxy progesterone, A 4 -androstene-3,17-dione, estradiol-17/3, estrone and pregnenolone (3/3-hydroxy-A 6 -pregnen-20-one).Quantitative measures of incorporation of radioactivity in these tissues indicate progesterone to be the major steroid formed in vitro in the human corpus luteum. (J Clin Endocr 24: 597, 1964)

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Section: Discussionmentioning

confidence: 77%

Steroid Hormone Formation in the Human Ovary: I. Identification of Steroids Formedin Vitrofrom Acetate-1-¹⁴C in the Corpus Luteum

Hammerstein

Rice

Savard

1964

The Journal of Clinical Endocrinology & Metabolism

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“…Studies on uterine tissues from rats (Marrone & Karavolas 1981, 1982, Redmond & Pepe 1986, guinea pigs (Glasier et al 1994, Hobkirk et al 1997, and humans (Bryson & Sweat 1967, 1969, Pollow et al 1975, Milewich et al 1977, Arici et al 1999, as well as placentae from humans (Little et al 1959) and goats (Sheldrick et al 1981), showed the presence of numerous P-converting enzymes. Similarly, incubations with ovarian tissues (especially granulosa cells) from rat (Zmigrod et al 1972, Lacy et al 1976, Nimrod 1977, de la Llosa-Hermier et al 1983, Moon et al 1986, Wiebe et al 1994a, human (Sweat et al 1960), and chicken (Marrone 1986, Wiebe et al 1990, as well as incubations with testicular cells or homogenates from trout (Andersson & Rafter 1990), frog (Canosa et al 1998), mouse (Kuwata et al 1976), rat (Slaunwhite & Samuels 1956, Wiebe 1978, Wiebe & Tilbe 1979, Wiebe et al 1980, Tilbe & Wiebe 1981, rabbit (Matsumoto et al 1976), and human (Savard et al 1956, Stegner & Lisboa 1984, have shown the presence in these tissues of a number of enzymes capable of converting P to a variety of products.…”

Section: Progesterone Is Metabolized By Many Tissuesmentioning

confidence: 99%

Progesterone metabolites in breast cancer

Wiebe¹

2006

Endocr Relat Cancer

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In the 70 years since progesterone (P) was identified in corpus luteum extracts, its metabolism has been examined extensively in many tissues and cell lines from numerous species. In addition to the reproductive tissues and adrenals, every other tissue that has been investigated appears to have one or more P-metabolizing enzyme, each of which is specific for a particular site on the P molecule. In the past, the actions of the P metabolizing enzymes generally have been equated to a means of reducing the P concentration in the tissue microenvironment, and the products have been dismissed as inactive waste metabolites. In human breast tissues and cell lines, the following P-metabolizing enzymes have been identified: 5a-reductase, 3a-hydroxysteroid oxidoreductase (3a-HSO), 3b-HSO, 20a-HSO, and 6a-hydroxylase. Rather than providing diverse pathways for inactivating and controlling the concentration of P in breast tissue microenvironments, it is proposed that the enzymes act directly on P to produce two types of autocrines/paracrines with opposing regulatory roles in breast cancer. Evidence is reviewed which shows that P is directly converted to the 4-pregnenes, 3a-hydroxy-4-pregnen-20-one (3a-dihydroprogesterone; 3aHP) and 20a-dihydro-progesterone (20aHP), by the actions of 3a-HSO and 20a-HSO respectively and to the 5a-pregnane, 5a-pregnane-3,20-dione(5a-dihydroprogesterone; 5aP), by the irreversible action of 5a-reductase. In vitro studies on a number of breast cell lines indicate that 3aHP promotes normalcy by downregulating cell proliferation and detachment, whereas 5aP promotes mitogenesis and metastasis by stimulating cell proliferation and detachment. The hormones bind to novel, separate, and specific plasma membrane-based receptors and influence opposing actions on mitosis, apoptosis, and cytoskeletal and adhesion plaque molecules via cell signaling pathways. In normal tissue, the ratio of 4-pregnenes:5a-pregnanes is high because of high P 3a-and 20a-HSO activities/expression and low P 5a-reductase activity/expression. In breast tumor tissue and tumorigenic cell lines, the ratio is reversed in favor of the 5a-pregnanes because of altered P-metabolizing enzyme activities/expression. The evidence suggests that the promotion of breast cancer is related to changes in in situ concentrations of cancerinhibiting and -promoting P metabolites. Current estrogen-based theories and therapies apply to only a fraction of all breast cancers; the majority (about two-thirds) of breast cancer cases are estrogeninsensitive and have lacked endocrine explanations. As the P metabolites, 5aP and 3aHP, have been shown to act with equal efficacy on all breast cell lines tested, regardless of their tumorigenicity, estrogen sensitivity, and estrogen receptor/progesterone receptor status, it is proposed that they offer a new hormonal basis for all forms of breast cancer. New diagnostic and therapeutic possibilities for breast cancer progression, control, regression, and prevention are suggested.

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“…It has been suggested (Sweat et al, 1960;Axelrod & Goldzieher, 1962) that 17a,20a-dihydroxyprogesterone could be cleaved to form Q9 steroids. However, only a limited amount of direct evidence for the side-chain cleavage to C19 steroids has been available for the testis (Berliner & Ellis, 1965).…”

Section: Recrystallization Ofproductsmentioning

confidence: 99%

Correlation between ultrastructure and biochemical changes in the testis of the American grey squirrel, Sciurus carolinensis, during the reproductive cycle

Pudney¹,

Lacy²

1977

Reproduction

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Summary. Distinct differences in the ability of isolated seminiferous tubules and interstitium to utilize steroid precursors for androgen production in vitro were observed during the reproductive cycle of the American grey squirrel, Sciurus carolinensis. In spermatogenically active testes, the seminiferous tubules and the interstitium readily synthesized androgens from labelled C21 steroid precursor; seminiferous tubules also produced significant amounts of 17\g=a\,20\g=a\-dihydroxyprogesterone.However, during sexual regression androgen synthesis was drastically reduced in both testicular components, while the production of 20\g=a\-reducedmetabolites of progesterone and 17\g=a\-hydroxyprogesterone was increased. Many of the fine-structural changes occurring in Leydig and Sertoli cells during the reproductive cycle could be correlated with the capacity of isolated seminiferous tubules and interstitium to formulate androgens from labelled precursors.

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The synthesis and metabolism of progesterone in the human and bovine ovary

Cited by 60 publications

References 21 publications

Steroid Hormone Formation in the Human Ovary: I. Identification of Steroids Formedin Vitrofrom Acetate-1-¹⁴C in the Corpus Luteum

Steroid Hormone Formation in the Human Ovary: I. Identification of Steroids Formedin Vitrofrom Acetate-1-¹⁴C in the Corpus Luteum

Progesterone metabolites in breast cancer

Correlation between ultrastructure and biochemical changes in the testis of the American grey squirrel, Sciurus carolinensis, during the reproductive cycle

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The synthesis and metabolism of progesterone in the human and bovine ovary

Cited by 60 publications

References 21 publications

Steroid Hormone Formation in the Human Ovary: I. Identification of Steroids Formedin Vitrofrom Acetate-1-14C in the Corpus Luteum

Steroid Hormone Formation in the Human Ovary: I. Identification of Steroids Formedin Vitrofrom Acetate-1-14C in the Corpus Luteum

Progesterone metabolites in breast cancer

Correlation between ultrastructure and biochemical changes in the testis of the American grey squirrel, Sciurus carolinensis, during the reproductive cycle

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Steroid Hormone Formation in the Human Ovary: I. Identification of Steroids Formedin Vitrofrom Acetate-1-¹⁴C in the Corpus Luteum

Steroid Hormone Formation in the Human Ovary: I. Identification of Steroids Formedin Vitrofrom Acetate-1-¹⁴C in the Corpus Luteum