Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia

  title={Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia},
  author={Christiaan F. Mooij and Silvia Parajes and Karijn J. Pijnenburg-Kleizen and Wiebke Arlt and Nils P. Krone and Hedi L Claahsen-van der Grinten},
  journal={Hormone Research in Paediatrics},
  pages={414 - 421}
Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to accumulation of steroid precursors and adrenal androgens. These steroids may have a biological effect on the steroid receptor with clinical consequences on diagnostics and treatment in CAH patients. Therefore, we analysed the effect of accumulated steroids [17-hydroxyprogesterone (17OHP), progesterone, androstenedione and testosterone] on aldosterone-mediated transactivation of the human mineralocorticoid… 

Figures from this paper

Adrenal Steroid Metabolites Accumulating in Congenital Adrenal Hyperplasia Lead to Transactivation of the Glucocorticoid Receptor.

21DF might have a clinically relevant agonistic effect on the hGR and could potentially partially compensate the cortisol deficiency in CAH patients, and thus may have glucocorticoid activity.

Interaction Between Accumulated 21-deoxysteroids and Mineralocorticoid Signaling in 21-hydroxylase Deficiency.

21-hydroxylase deficiency (21OHD) is a rare genetic disorder in which salt-wasting syndrome occurs in 75% of cases, due to inability to synthesize cortisol and aldosterone. Recent mass spectrometry

A Rationale for Mineralocorticoid Supplementation in Classic Congenital Adrenal Hyperplasia

  • P. Speiser
  • Medicine, Biology
    Hormone Research in Paediatrics
  • 2015
In this set of in vitro studies, the investigators delineate the nature of 17-hy-droxyprogesterone and progesterone interference with the ability of aldosterone to transactivate the mineralo-corticoid receptor (MR), which occurs at the level of recep-tor transactivation, rather than nuclear translocation.

Cardiovascular health, growth and gonadal function in children and adolescents with congenital adrenal hyperplasia

Treatment of children and adults with CAH requires an individualised approach and careful monitoring for early signs of complications is already warranted during paediatric healthcare provision to prevent and reduce the impact of comorbidities in later life.

Management challenges and therapeutic advances in congenital adrenal hyperplasia

Challenges in the management of congenital adrenal hyperplasia arise from multiple hormonal imbalances, the intrinsic tendency of the CAH-affected adrenal gland to overproduce androgens and limited treatment options, which often necessitate glucocorticoid excess.

Congenital adrenal hyperplasia: clinical and biochemical consequences of elevated adrenal steroid precursors

In untreated NC-CAH children growth acceleration is small and generally not visible in their growth charts, therefore, the absence of an increase in growth velocity does not exclude the diagnosis NC- CAH.

Selective Progesterone Receptor Modulators—Mechanisms and Therapeutic Utility

Mifepristone, ulipristal acetate, vilaprisan, and asoprisnil effectively treated heavy menstrual bleeding in patients with uterine fibroids, but limited data exist regarding the efficacy of SPRMs for HMB outside this context.

Clinical outcomes and characteristics of P30L mutations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Outcome studies of CAH have confirmed the uniqueness of this mutation such as difficulties in phenotype classification, different fertility, growth, and psychologic issues in comparison with other genotypes, and different mechanisms for increased androgenization in patients carrying P30L mutation.

Treatment of congenital adrenal hyperplasia in children aged 0–3 years: a retrospective multicenter analysis of salt supplementation, glucocorticoid and mineralocorticoid medication, growth and blood pressure

All children showed an increase in BMI-SDS and a high rate of BP readings >P95 until 3 years, indicating the start of weight gain and negative effects on blood pressure already in very early life.



Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor.

17alpha-OH-P is a strong hMR antagonist and could exacerbate mineralocorticoid deficiency in patients with congenital adrenal hyperplasia, and progesterone metabolism to these compounds is a possible protective mechanism for hMR.

Interaction of synthetic progestagens with renal mineralocorticoid receptors.

The decreased affinity of synthetic progestins for mineralocorticoid receptors explains in part the lack of natriuretic activity of these compounds.

Transactivation via the human glucocorticoid and mineralocorticoid receptor by therapeutically used steroids in CV-1 cells: a comparison of their glucocorticoid and mineralocorticoid properties.

9alpha-fluorocortisol, the most frequently used steroid for MC substitution, seems to be the best choice of available steroids for this purpose.

Circadian patterns of plasma cortisol, 17-hydroxyprogesterone, and testosterone in congenital adrenal hyperplasia.

It is concluded that single 17-hydroxyprogesterone values are unlikely to give adequate information about the quality of treatment in children with congenital adrenal hyperplasia.

The Intracellular Localization of the Mineralocorticoid Receptor Is Regulated by 11β-Hydroxysteroid Dehydrogenase Type 2*

Evidence is provided that 11 β-HSD2, besides inactivating 11β-hydroxyglucocorticoids, functionally interacts with the MR and directly regulates the magnitude of aldosterone-induced MR activation.

The metabolic effects of progesterone in man.

It has been demonstrated that progesterone induces growth in the sebaceous glands of rats, and in a man with Addison's disease who was maintained with added salt, 30 mg.

Transactivation and synergistic properties of the mineralocorticoid receptor: relationship to the glucocorticoid receptor.

Experiments revealed that the hMR amino-terminus does not provide the strong transactivation function present in the equivalent hGR domain and, in contrast to the hGR amino- terminus, interferes with the synergistic activity mediated by the DNA- and ligand-binding domains of both receptors.

A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness.

The findings reveal that cortisol and heart rate responses to a psychosocial stressor are enhanced in carriers of the MR180V variant.