Relationships between chemical structure and biological properties of progestogens

Rozenbaum, H

doi:10.1016/s0002-9378(16)32477-2

Cited by 24 publications

(7 citation statements)

References 34 publications

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“…During the cyclic passage through the liver, estrogens are degraded to less active metabolites. 14 In experiments with ovariectomized (OVX) rats, it has been suggested that endogenous conversion of certain progestogens to biologically significant amounts of estrogen metabolites may occur in the gastrointestinal tract or in the liver. 14 Post-mitotic tissues of highenergy demand are at greater risk of damage by free radicals, consistent with the notion where signs of oxidative damage usually start to appear at these body sites.…”

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confidence: 99%

Effects of estrogens on oxidative protein damage in plasma and tissues in ovariectomised rats

Topçuoğlu¹,

Uzun²,

Balcı³

et al. 2009

CIM

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Purpose: To assess estrogen-related changes in the redox status of the brain and liver proteins as well as the systemic oxidative stress in ovarectomised (OVX) rats Methods: Twelve-week-old, sexually mature female Sprague–Dawley rats (200-250g) were randomly divided into four groups: The following treatment combinations were administrated daily to all in 0.05 ml 96% ethanol solution by gastric gavage. (1) Sham operation (2) OVX rats (3) OVX rats [0.02 mg/kg/day of 17?-estradiol (E2) and 0.01 mg/kg/day of norethisterone acetate] (4) OVX rats [E2 (0.01 mg/kg/day) and drospirenon (0.02 mg/kg/day)]. Estrogen levels were determined using routine clinical-chemistry methods. We also measured protein oxidation parameters such as protein carbonyl (PCO), total thiol (T-SH) and the other oxidative stress markers malondialdehyde (MDA) and glutathione (GSH). Results: Ovariectomy resulted in abnormal elevation of plasma and tissue oxidative stress markers and changes in redox status of the proteins in tissue dependent manner. Supplementation of various estrogens combinations partially alleviated these abnormalities and restored redox homeostasis of proteins after the ovariectomy. Among the studied protein oxidation parameters, plasma and tissue PCO levels of the OVX rats were higher than those of the control groups (P < 0.01). Hormone replacement therapies (HRT) caused a decrease in PCO and MDA in both plasma and tissue of the OVX rats (P < 0.01). HRT in OVX rats decreased plasma MDA and increased liver and brain GSH (P < 0.01). Liver MDA levels of the Drospirenon-treated rats were lower than in the norethisterone acetate group (P < 0.01). On the other hand, Drospirenon increases brain GSH s more effectively than norethisterone acetate (P < 0.01). After bilateral oopherectomy, plasma and tissue T-SH levels decreased in the OVX group compared with control (P < 0.01). Norethisterone acetate increased plasma T-SH more effectively than Drospirenon (P < 0.05) Conclusions: The study showed the extent of oxidative protein damage (OPD) in this model of estrogen deficiency. The protective effect of estrogens against tissue specific OPD suggests that estrogens play an important role within the antioxidant defense systems in plasma, liver and brain. The exact molecular mechanisms leading to these findings are not yet completely known. Meanwhile, hormone replacement therapy for the prevention of OPD in a tissue specific manner may be required.

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confidence: 99%

Effects of estrogens on oxidative protein damage in plasma and tissues in ovariectomised rats

Topçuoğlu¹,

Uzun²,

Balcı³

et al. 2009

CIM

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“…The anabolic properties of these progestins may relate to their structural similarity to testosterone which is known to stimulate skeletal muscle protein synthesis, an action that is independent of the anabolic effects of insulin (Kochakian and Costa 1959;Hager and Kalkhoff 1989). It is also of interest that most progestins of the nortestosterone type do bind to tissue androgen receptors (Rozenbaum 1982).…”

Section: Discussionmentioning

confidence: 99%

Levonorgestrel and Norethindrone Alter Insulin Action on Skeletal Muscle of the Female Rat

Hager

Kalkhoff²

1990

Horm Metab Res

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Prospective studies of women receiving oral contraceptives suggest that the progestin component may induce insulin resistance and variable deterioration of glucose tolerance. Because the tissue sites and nature of this insulin antagonism are not well-defined, we studied the effects of two parenterally administered progestins, levonorgestrel (NG) and norethindrone (NE), on insulin-regulated glucose uptake and phenylalanine release by the perfused rat hindquarter. Female rats were injected sc for 14 days with NG or NE (10 or 30 micrograms/kg/day). Low-dose NG and high-dose NE approximate the per kg dose received by women taking a high-dose progestin oral contraceptive. Phenylalanine release and glucose uptake (nmole/min/g) by the perfused hindquarters were calculated from the A-V difference for each. Progestin treatment (30 micrograms/kg/d) significantly reduced phenylalanine release from hindquarters perfused without exogenous insulin. Hindquarters from the high dose NG and low and high dose NE rats perfused with insulin (100 microU/ml) released 22% less phenylalanine than control rats perfused with the same insulin concentration (P less than 0.01) but the net suppression below baseline was similar in the control and steroid-treated groups. High-dose progestin treatment did not alter glucose uptake by hindquarters perfused without exogenous insulin. Insulin (100 microU/ml) increased glucose uptake by hindquarters of control and progestin-treated rats as compared to animals in the same treatment group perfused without exogenous insulin (P less than 0.01). High dose NE impaired insulin-stimulated glucose uptake 24% below values of the control group (P less than 0.01). The other NE and NG doses had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…All progestogens bind to progesterone receptors, depending on their individual structures. They also bind to other receptors, such as androgen or corticosteroid receptors [77]. It seems as if MPA acts partly through androgen receptors when inducing gonadotropin suppression [72].…”

Section: Longacting Injectablesmentioning

confidence: 99%

Mechanism of action of gestagens

Landgren

1990

Intl J Gynecology & Obste

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In the mid-1950s it was shown that ovulation can be inhibited by oral administration of progesterone or of synthetic progestogens such as norethynodrel. The idea that progestogens may interfere with fertility even when administered in doses so small, that they do not invariably inhibit ovulation was launched in the mid-1960s by a group of Mexican investigators. Since then a large number of studies have been conducted on the mechanism of action of gestagens when used as contraceptives. The objective of this communication is to review the information collected so far on this topic.

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Relationships between chemical structure and biological properties of progestogens

Cited by 24 publications

References 34 publications

Effects of estrogens on oxidative protein damage in plasma and tissues in ovariectomised rats

Effects of estrogens on oxidative protein damage in plasma and tissues in ovariectomised rats

Levonorgestrel and Norethindrone Alter Insulin Action on Skeletal Muscle of the Female Rat

Mechanism of action of gestagens

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