#steroidogenesis

[toxicseminar]

In my previous post, when asked what causes the reproductive changes Dr. David Skelly states, “I don’t know.” I wanted to look up more research on the mechanism of action for atrazine to “feminize” male frogs. I found this article published by Dr. Tyrone Hayes that explains that atrazine can feminize ZZ frogs if they are exposed to significantly high level at metamorphosis as atrazine induces the production of aromatase. Aromatase is the enzyme responsible for catalyzing the conversion of testosterone to estrogen (in steroidogenesis)  

-ATG

[ijtsrd]

Computational prediction of damage associated non synonymous SNPs of CYP17A1 and CYP19A1 gene

By Richa Bhatnager | Ranjeet Kaur | Amita Suneja Dang | Twinkle Dahiya"Computational prediction of damage associated non synonymous SNPs of CYP17A1 and CYP19A1 gene" 

Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-1 | Issue-6 , October 2017, 

URL: http://www.ijtsrd.com/papers/ijtsrd3581.pdf  

http://www.ijtsrd.com/biological-science/biotechnology/3581/computational-prediction-of-damage-associated-non-synonymous-snps-of-cyp17a1-and-cyp19a1-gene/richa-bhatnager

multidisciplinary journal, call for paper life sciences, ugc approved management journal

The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. CYP17A1 and CYP19A1 are the key proteins involved in steroidogenesis. Majority of polymorphisms have yet not been evaluated for their possible damaging effects on protein structure and function of both the genes. In present analysis, we tried to find out the effect of damage associated nsSNPs of both CYP17A1 and CYP19A1 gene by using various computational algorithms. Out of 205 and 246 nsSNPs reported for CYP17A1 and CYP19A1 gene, total 13 and 7 were predicted to affect the structure and function respectively. R125Q, R416H and F453S substitutions of CYP17A1 gene were not reported previously hence provide the new dataset of unexplored SNPs for their validation. By our results we also found that substitution of mainly Arginine or Phenyl alanine within conserved domain of redox binding, heam binging and redox partner site would cause partial or complete loss of function of both CYP17 and CYP19 gene. 

[testecoeur]

The two cells hypothesis

A. The preovulatory follicle produces estradiol through a paracrin interaction between the theca and granulosa cells. Theca cells provide the granulosa cells with androstenedione in order to produce estradiol. Granulosa cells express the right enzymes that convert androstenedione to estradiol (P450 aromatase, 17β hydroxysteroid dehydrogenase1). 

B. In corpus luteum, granulosa cells obtain vessels, LH receptors and enzymes for progesterone synthesis. Theca cells are the source of androstenedione that is necessary for the production of estradiol in granulosa cells. Gonadotropins, steroidogenic factor 1 (SF-1) and steroidogenic acute regulatory protein (StAR) have fundamental functions in ovarian steroidogenesis. (ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; FSH-R, follicle stimulating hormone receptor; LH-R, luteinizing hormone receptor; P450 arom, P450 aromatase; 17β-HSD-I, 17-β hydroxysteroid dehydrogenase-I). (with permission of Larsen et al., eds. The physiology and pathology of the female reproductive axis. En: Williams Textbook of Endocrinology. Saunders; 2003; 604.)

From: Greenspan Endocrinologia Basica y Clinica Novena Edición, 2012 McGraw Hill; Translated from the ninth English edition of: Greenspan´s Basic & Clinical Endocrinology Copyright © 2011 by The McGraw-Hill Companies, Inc.

[medicalwatson]

Adrenal Disorders pt. 2

This post will be about Congenital Adrenal Hyperplasia (CAH)

Let's break down what this actually means:

Congenital - present from birth

Adrenal - of or relating to the adrenal glands

Hyperplasia - enlargement of an organ or tissue 

In essence, this is a genetic condition that results in swelling of the adrenal glands. It is autosomal recessive.

There are many different forms of CAH; the problem is that there are mutations in genes for enzymes mediating the steroidogenic pathway. The most common of these is 21 hydroxylase. Throughout this post we'll refer back to the diagram below:

This is a diagrammatic representation of the steroid synthesis pathway. The enzyme 21 hydroxylase is in bold here, but the others will be important later. So, 21 hydroxylase - it can be either complete or partial

Complete 21 hydroxylase deficiency 

Looking at the diagram, which hormones will be totally absent? Well, 21 hydroxylase is essential in the formation of cortisol and aldosterone, so both of these hormones will be totally absent. That's pretty bad. Like, you'll die within 24 hours bad. Conversely, the sex steroids and testosterone are present in excess.

What age might someone with this condition present? They may present as a neonate with what's known as salt-losing Addisonian crisis. They may also present before birth, in utero. At birth, girls may have ambiguous genitalia, having been virilised (development of male characteristics in a girl) by adrenal testosterone excess.

Partial 21 hydroxylase deficiency

This is similar to the above, though not as severe. Both cortisol and aldosterone are deficient and the sex steroids and testosterone are in excess. People with this condition may present at any age as they survive.

The main problem in partial 21 hydroxylase deficiency is hirsuitism (excessive hair growth) and virilisation in girls and precocious puberty (i.e. puberty earlier than normally expected) in boys due to the adrenal testosterone excess.

Before going onto the next enzyme deficiency, it's important to make note of something: 11-deoxycorticosterone has aldosterone-like (mineralocorticoid) effects, which means it can cause hypertension and hypokalaemia in excess. Just keep that in mind.

11-beta hydroxylase deficiency 

You can see from the diagram above that both cortisol and aldosterone are deficient. However, this time not only are the sex steroids and aldosterone present in excess, but also 11-deoxycorticosterone! Remember what we just said? No? Scroll up and read it again, then! This means that as well as virilisation, a patient may experience hypertension and hypokalaemia (just as aldosterone would do in excess).

And finally...

17-alpha hydroxylase deficiency 

Slightly different situation here. You can see the 17 hydroxylase is towards the start of the pathway - hopefully you can also see that this means aldosterone will be spared, but cortisol and the sex steroids will be deficient. Not only is aldosterone spared; it is present in excess due to the build up of its precursors - this includes 11-deoxycorticosterone. These are both mineralocorticoids, so you can guess the problems: hypertension and hypokalaemia!

The patient will also experience sex steroid deficiency and low glucose - this is due to the glucocorticoid deficiency (cortisol raises blood glucose levels).

And that's a quick rundown of Congenital Adrenal Hyperplasia. Hope you enjoyed it!

Watson