For the GG's, PCOS,
Caution-technical info ahead, but hey, I put the
eck in ech (aka-t'ech'nical, lol).
PCOS is a complex disorder of unknown etiology, and it involves several specialists for presenting reproductive, endocrinologic, dermatological, gynecological, cardiac and psychological implications.
Hyperinsulinemia seems to be one of the main factors responsible for steroidogenesis deregulation.
The variable and heterogeneous clinical picture makes diagnosis of PCOS difficult and tends to delay management that could avoid late complications.
Its treatment is preventive and aims to maintain the endometrial healthy, to antagonize the actions of androgens in target-tissues, to reduce insulin resistance (IR) and to correct anovulation. In addition to combined contraceptives and antiandrogens, the insulin-sensitizing agents are effective in preventing diseases associated with hyperinsulinemia. It is difficult to explain the therapeutic success of metformin in reducing insulin and androgen levels, as observed in some studies. It may be related to genetic variations, body weight, life style, duration of treatment and dosage of the drug.
Today, in order to avoid late complications, the specialists share investigations, trying to understand the etiology and pathophysiology of PCOS, which are essential for its treatment. The main focus of these studies has been several genetic and environmental determinants of the syndrome, for reflecting its heterogeneous phenotype.
The androgens derive from cholesterol and, in females, are synthetized by the ovaries, adrenal glands and in extraglandular sites of steroid conversion (liver, muscles, skin and adipose tissue).29,30 Androgen aromatization occurs in muscle and adipose tissues, that is, testosterone (T) and androstenedione (A) are converted into estrogens - estrone and estradiol, whereas, in the pilosebaceous unit and skin, T is converted into dihydrotestosterone (DHT) by the enzyme 5-alpha-reductase 1 or 2 (Figure 1B).29
The pilosebaceous unit and skin represent target-structures for androgen, which explains the pathophysiology of hyperandrogenism cutaneous manifestations (hirsutism, acne, seborrhea and alopecia).2
3-alpha-androstenediol glucuronide (3a diol G) derives from the conversion of DHT and A, by means of 5a-redutase. It is considered a marker of androgen biological action in the pilosebaceous unit, and the skin its main production site.2,4,29,30
Androgen biosynthesis (Figure 2) is mediated by cytochrome P-450c-17, an enzyme with 17a-hidroxylase, 17, 29-lyase and 17b-hydroxysteroid dehydrogenase (17b HSD or 17b R) activities. The androgens (A and T) are aromatized to estrone by the enzyme aromatase (cytochrome p-450 aromatase).27,29,31
In the ovaries, the androgens are precursors of estrogens and their production is controlled by LH/FSH (Figures 1Aand 2, and Chart 2).29,30,32 Normal ovarian function is determined by a combined action of LH in the theca cells, corpus luteum and stroma, and of FSH in granulosa cells.28
3. The role of insulin
Insulin is a polypeptide secreted by b-cells of the pancreas, and play an important role in glucose homeostasis.4,19,31 The classic target tissues include liver, muscles and adipose tissue. The terms insulin sensitivity and insulin resistance (IR) refer to the action of insulin in glucose homeostasis.4,19,31
4. Peripheral increase in cortisol metabolism
Increased androgen production by adrenal glands is observed in 25% of PCOS patients,70 probably as a result of genetic influence or secondary to abnormal secretion of ovarian androgens.31,65
Hyperandrogenism and skin: polycystic ovary syndrome and peripheral insulin resistance*
http://www.scielo.br/scielo.php?pid=S0365-05962005000400011&script=sci_arttext&tlng=en
(yes, that's four, j/k)