Progestational and androgenic receptor binding affinities and in vivo activities of norgestimate and other progestins

Phillips, A.; Demarest, Keith T.; Hahn, Do Won; Wong, Frankie A.; McGuire, J.L.

doi:10.1016/0010-7824(90)90039-x

Cited by 119 publications

(28 citation statements)

References 9 publications

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“…Variation in the potency of progestogens is mainly due to their different binding affinities to the progesterone receptor [1]. Progestogens are used in concert with estrogen for endometrial protection during postmenopausal hormone therapy (HT).…”

Section: Introductionmentioning

confidence: 99%

The Role of Progestogens in Regulating Matrix Metalloproteinase Activity in Macrophages and Microglial Cells

2011

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Although the systemic effects of progestogens have been extensively studied, little is known in regards to the cellular effects of these compounds. Using a cellular model for vascular (macrophages) and brain (microglial) cells, we studied the effects of various progestogens, either alone or in combination with 17β-estradiol (E(2)) on the activity of matrix metalloproteinase-9 (MMP-9), a proteolytic enzyme involved in vascular remodeling and plaque destabilization in cardiovascular events, blood-brain barrier breakdown in stroke and brain regeneration and neurovascular remodeling during repair phases of brain injury. In the absence of E(2), medroxyprogesterone acetate (MPA), a synthetic progestogen and progesterone (PG) metabolites tended to increase MMP-9 enzyme activity in macrophages and microglial cells, whereas PG decreased such activity in macrophages; exceptions being that MPA and the PG metabolite, pregnanediol (Pdiol) had no effect on macrophage MMP-9 enzyme activity and PG had no effect on microglial cell MMP-9 enzyme activity. In the presence of E(2), an opposite affect was observed whereby MPA and the PG metabolites tended to decrease MMP-9 enzyme activity from macrophages and microglial cells, whereas PG had no effect; exceptions being that MPA and Pdiol had no effect on macrophage MMP-9 enzyme activity. In conclusion, these results demonstrate that the effects of PG, PG metabolites and MPA on MMP-9 enzyme activity differ across vascular and brain cells when administered alone or in combination with E(2) which could have important mechanistic implications for hormone therapy.

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Section: Introductionmentioning

confidence: 99%

The Role of Progestogens in Regulating Matrix Metalloproteinase Activity in Macrophages and Microglial Cells

2011

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“…LD-OCs commonly include a little androgen activity at various concentrations [3]. Tri-Norinyl has the androgen activity of 0.23 mg per one cycle as methyltestosterone amount [4].…”

Section: Discussionmentioning

confidence: 99%

Alopecia related to low dose oral contraceptive

Yokoyama

Sato

Saito

2002

Arch Gynecol Obstet

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“…They exert rapid non-genomic effects on Leydig cells, spermatozoa and affect sperm function (Lishko et al, 2011;Strunker et al, 2011) such as motility, capacitation, acrosome reaction and the ability to bind to zona proteins (Baldi et al, 1995(Baldi et al, , 1999. Some progestins, like LNG, also bind to androgen receptors (Phillips et al, 1990;Kumar et al, 2000) and exert androgenic activities such as decreasing blood sex hormone binding globulin and HDL-cholesterol levels. Clinical studies showed that combining progestins with androgens lead to an enhanced suppression of gonadotropins and spermatogenesis by inhibiting spermatogonial proliferation and spermiation in the human testes (McLachlan et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Functional role of progestin and the progesterone receptor in the suppression of spermatogenesis in rodents

et al. 2013

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SUMMARYSynthetic progestins such as levonorgestrel (LNG) are used in combination with testosterone (T) in male contraceptive clinical trials to suppress gonadotropins secretion, but whether progestins have additional direct effects on the testis are not known. This study aimed to examine the effect of a potent progestin, (LNG), alone or in combination with testosterone (T) on spermatogenesis in adult rats, and to evaluate the functional role of the progesterone receptors (PRs) in the testis. In comparison with a low dose of LNG treatment in adult rats for 4 weeks, T and T + LNG treatment decreased testicular sperm count to 64.1 and 40.2% of control levels respectively. LNG induced germ cell apoptosis at stages I-IV and XII-XIV; T increased apoptosis at stages VII-VIII; LNG + T treatment induced greater germ cell apoptosis at a wider range of seminiferous epithelial stages. RT-PCR and Western Blots showed that PR was present in testes and up-regulated during suppression of spermatogenesis induced by testicular hormonal deprivation. PR knockout (PRKO) mice had larger testes, greater sperm production, increased numbers of Sertoli and Leydig cells. Suppression of gonadotropin and intratesticular T by GnRH-antagonist treatment induced PR promoter driven LacZ expression in Leydig cells of PRKO mice. This suggests that GnRH-antagonist treatment while inducing germ cell apoptosis also up-regulates PR. We conclude that (i) LNG + T induced greater suppression of spermatogenesis through increase in germ cell apoptosis involving a wider range of seminiferous epithelial stages than either treatment alone, (ii) up-regulation of PR was associated with inhibition of spermatogenesis, (iii) PR knockout mice showed increased sperm production suggesting that testicular PR activated events play a physiological and pharmacological inhibitory role in the testis. These data support the hypothesis that in addition to its known suppressive effects on gonadotropins, progestins may have direct inhibitory actions on the testis.

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Progestational and androgenic receptor binding affinities and in vivo activities of norgestimate and other progestins

Cited by 119 publications

References 9 publications

The Role of Progestogens in Regulating Matrix Metalloproteinase Activity in Macrophages and Microglial Cells

The Role of Progestogens in Regulating Matrix Metalloproteinase Activity in Macrophages and Microglial Cells

Alopecia related to low dose oral contraceptive

Functional role of progestin and the progesterone receptor in the suppression of spermatogenesis in rodents

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