Effects of nomegestrol acetate administration on central and peripheral beta-endorphin and allopregnanolone in ovx rats

Lenzi, E; Pluchino, Nicola; Begliuomini, Silvia; Ninni, Filippo; Freschi, Letizia; Centofanti, M.; Casarosa, Elena; Luisi, Stefano; Valentino,; Luisi, M; Genazzani, Ar

doi:10.1016/j.jsbmb.2008.02.002

Cited by 20 publications

(9 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The administration of estradiol valerate confirming the results obtained in our previous studies, reversed the decline in the levels of both allopregnanolone and ␤-endorphin induced by ovariectomy in all analyzed brain areas except for the adrenal gland [18][19][20][21][22].…”

Section: Discussionsupporting

confidence: 90%

Central modifications of allopregnanolone and β-endorphin following subcutaneous administration of Nestorone

Lenzi

Pluchino

Begliuomini

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 90%

Central modifications of allopregnanolone and β-endorphin following subcutaneous administration of Nestorone

Lenzi

Pluchino

Begliuomini

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

View full text Add to dashboard Cite

“…Ovariectomy significantly reduces circulating as well as brain concentrations of hormonal factors known to effect mood, such as allopregnanolone and beta-endorphin [33,34]. In female OVX Wistar rats, oral NOMAC (0.5 and 1 mg/kg/day) significantly increased allopregnanolone in the hippocampus, but not in other areas of the brain [34].…”

Section: Resultsmentioning

confidence: 99%

Preclinical pharmacological profile of nomegestrol acetate, a synthetic 19-nor-progesterone derivative

Diepen

2012

Reprod Biol Endocrinol

View full text Add to dashboard Cite

BackgroundNomegestrol acetate (NOMAC), a synthetic progestogen derived from 19-nor-progesterone, recently completed clinical trials for use with 17beta-estradiol in a new monophasic combined oral contraceptive. In this review, published as well as previously unpublished preclinical studies that detail the effects of NOMAC on estrogenic, progestogenic, and androgenic systems, as well as mineralocorticoid, glucocorticoid, bone, and metabolic indices are described.MethodsIn vitro assays to determine NOMAC structure-activity relationships used tissue derived from rat uteri. Transactivation profiles were performed using Chinese hamster ovary (CHO) cells transfected with cDNAs encoding human steroid receptors. Estrogenic and anti-estrogenic activities were monitored in vivo in rats as well as in vitro in human breast cancer cells. Standard in vivo techniques were used in rats to determine progestational activity; antigonadotropic, androgenic, mineralocorticoid, and glucocorticoid activities; as well as effects on bone and other metabolic indices. Ovulation inhibition was monitored in rats and primates. NOMAC’s effects on cardiovascular systems were determined in dogs and primates.ResultsNOMAC was without significant agonistic or antagonistic activity for estrogen receptor alpha or beta in vitro, and inhibited ovulation in rats and monkeys (2.5 mg/kg and 1 mg/kg, respectively). NOMAC lacked androgenic, antimineralocorticoid, glucocorticoid, and metabolic activity and exhibited moderate anti-androgenic activity in rats. NOMAC did not affect bone mineral density (BMD) in rats or hemodynamic and electrophysiologic parameters in dogs and primates.ConclusionsNOMAC is a selective progestogen structurally similar to progesterone that has modest anti-androgenic activity and does not affect lipid or carbohydrate metabolism, BMD, or many cardiovascular parameters in selected animal models.

show abstract

“…NOMAC, derived from 19-nor-progesterone, suppresses the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus and inhibits the production of progesterone from ovaries (10). It was shown in animal studies that NOMAC increases the production of ALLOPREG, which plays an important role in the coordination between neurons and supporting cells, which are required for producing myelin sheaths (11). It is well documented that the mechanism of action of progestin only pills (POPs) is basically related to their progestogenic effect of thickening the cervical mucus, and thinning of the endometrium causes it to become involuted.…”

Section: Ms Sex Steroids Hormonal Contraceptive Methodsmentioning

confidence: 99%

Multiple sclerosis; a disease of reproductive-aged women and the dilemma involving contraceptive methods

Türkyılmaz¹,

Yıldırım²,

Avşar³

2015

J Turkish German Gynecol Assoc

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an autoimmune disorder characterized by chronic inflammation in the central nerves system and subsequent demyelination of nerves (1).The disease predominantly affects women of reproductive ages in the 3 rd and 4 th decades; 62% of these women use contraceptive methods (2, 3). There are recent conflicting studies about the effect of oral contraceptive (OC) use on MS and MS-like symptoms in the literature (4, 5). Therefore, it is important to understand the effects of hormonal contraceptives in MS patients. In addition, the medical treatments of MS such as through the use of interferons (IFNs), fingolimod, dimethyl fumarate, and, natalizumab may compromise the pregnancy in patients with this disease (6). The ongoing use of IFNs in women planning pregnancy may also be relatively contraindicated because of possible abortifacient properties (6). Therefore, the use of contraceptive methods to avoid unintended pregnancies will be extremely important in MS patients, particularly during the relapse phase of the disease or the time when the disease is not completely under control. Therefore, clinicians usually try to provide contraceptive counseling to these young MS patients for addressing the question regarding the most appropriate contraceptive method. Providing an appropriate contraception options to MS patients is one of the most challenging issues for clinicians to deal with. However, most contraceptives methods are hormonal methods, and recent studies have raised questions about their potential adverse effects on the disease. We start this review by discussing the use of hormonal contraceptives in MS patients. To understand the effect of hormonal contraceptives on MS, the effects of sex steroids on this disease are discussed initially. MS, sex steroids, hormonal contraceptive methodsAlthough the strong interaction between the pathogenesis of MS and the immune system and sex steroids is well known for a long time, the exact mechanism through which the disease develops is yet to be identified completely. Hormonal contraceptives are effectively used by many young women to prevent unintended pregnancies. Most women use this method, particularly in their middle reproductive years, in which MS is mostly detected. The well-recognized problem in the pathogenesis of MS is inflamMultiple sclerosis (MS) is an autoimmune disorder characterized by chronic inflammation in the central nerves system. Because the disease predominantly affects women of reproductive ages, having knowledge about contraception options for MS patients can make clinicians provide better counseling. Although most contraceptive methods are generally accepted as safe and effective in MS patients, recent studies have raised questions about their potential adverse effects on the disease. The use of contraceptive methods to avoid unintended pregnancies is crucial in MS patients, particularly during the relapse phase of the disease or the time when the disease is not completely under control. This review investigates the contraception...

show abstract

Effects of nomegestrol acetate administration on central and peripheral beta-endorphin and allopregnanolone in ovx rats

Cited by 20 publications

References 25 publications

Central modifications of allopregnanolone and β-endorphin following subcutaneous administration of Nestorone

Central modifications of allopregnanolone and β-endorphin following subcutaneous administration of Nestorone

Preclinical pharmacological profile of nomegestrol acetate, a synthetic 19-nor-progesterone derivative

Multiple sclerosis; a disease of reproductive-aged women and the dilemma involving contraceptive methods

Contact Info

Product

Resources

About