Commentary Open Access Sandhu et al., J Steroids Hormon Sci 2013, S4 DOI: 10.4172/2157-7536.S4-001 J Steroids Hormon Sci Neurosteroids ISSN:2157-7536 JSHS an open access journal Keywords: Tetrahydrodeoxycorticosterone; Allopregnanolone; Pregnancy; Postpartum period; Neuroactive steroid; Depression Introduction Neurosteroids like tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALP) are metabolites of steroids and formed by the action of 5α-reductase type-1 and 3α-hydroxysteroid dehydrogenase enzymes [1,2]. THDOC and ALP has anticonvulsant, anxiolytic, sedative efects [3,4] and induces behavioural/health changes during pregnancy and menstruation while, anxiety and depression in epilepsy [5-9]. Neuroactive steroids are manufactured in the neurons, astrocytes and glial cells and can be produced from the same tissue [10]. Te γ-aminobutyric acid (GABA) system is one of the many inhibitory systems and present in about 25% of the brain receptors [11]. Tere are three types of GAB A receptors viz. GABA A , GABA B and GABA C . Both of these neuroactive hormones are GABA A receptor agonist which is pentameric and has an ion channel in its center [12]. Barbiturates are also GABAA agonist, and these anesthetics inhibit ovulation in rats [13]. Tere is also a known correlation of ALP and THDOC with GnRH, LH and FSH [14]. Since, there are few studies on the function and working of ALP and THDOC, however, the correlation of neurosteroid infuencing the pregnancy and postpartum period is not yet well known. It is likely that GABAergic progesterone metabolites work singularly or coordinal to induce physiological/pathologic efects. What is allopregnanolone? ALP is a 3α-hydroxy-A ring-reduced steroid. It is synthesized de novo either in brain [15], in the adrenal gland cortex [10,16], and in corpus luteum during the ovulatory menstrual period [17]. Te alteration in physiological rhythms of progesterone depends upon stress, stage of menstrual cycle, menopause, and pregnancy. When there is sudden decrease in body progesterone before premenstrual bleeding is the cause of premenstrual syndrome with similar symptoms in the postmenopausal women [18,19]. ALP levels gets higher during early and postmenopausal women receiving dehydroepiandrosterone and the values get as much higher as are pragmatic in pregnancy [20]. Tis steroid metabolite exerts neuromodulatory possessions in CNS and is a GABA A receptor agonist that afects mood, modulating anxiety, and memory [21,22]. Tere is a positive correlation between body ALP levels and the level of progesterone [23,24]. In estrus cycle, the body ALP level diverges with the change in phases of estrus. During luteal phase the level of ALP is about four times higher than the follicular phase [25] and gets at its peak with the advancement in pregnancy [24]. Animal studies show that the ALP levels remain elevated in the brain than blood circulation [16]. Afer the exposure to stress there is an increase of circulating ALP [25] than the normal calm and quite state, however, in adrenalectomized rats [10] the concentration of ALP remained undetectable in the plasma. What is THDOC? An increased activity of hypothalamic-pituitary-adrenal (HPA)- axis is due to more production of corticotropin releasing hormone (CRH), which is a key arbitrator of CNS stress [26]. Afer acute stress the hypothalamus production of CRH increases that prompts the discharge of ACTH from the anterior pituitary gland, which ultimately excites cortex of the adrenal for the production of glucocorticoids and neuroactive steroid precursors [27]. Tere are two types of glucocorticoids present eg. cortisol (human & non-human primates) and corticosterones (rodents); these give negative feedback upon *Corresponding author: Mansur A Sandhu, Department of Veterinary Biomedical Sciences, Faculty of Veterinary and Animal Sciences, PMAS, Arid Agriculture University, Rawalpindi, Pakistan, Tel: +92-321-7830305; E-mail: mansoorsandhu@uaar.edu.pk Received November 22, 2013; Accepted December 19, 2013; Published December 26, 2013 Citation: Sandhu MA, Anjum MS, Mukhtar N, Hussain R, Khan IA (2013) Does Interrelationship of Allopregnanolone and Tetrahydrodeoxycorticosterone during Pregnancy and Postpartum Depression Exist? A Review of the Current Evidence. J Steroids Hormon Sci S4: 001. doi:10.4172/2157-7536.S4-001 Copyright: © 2013 Sandhu MA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Does Interrelationship of Allopregnanolone and Tetrahydrodeoxycorticosterone during Pregnancy and Postpartum Depression Exist? A Review of the Current Evidence Mansur A Sandhu 1 *, Muhammad S Anjum 1 , Nasir Mukhtar 1 , Riaz Hussain 1 and Imtiaz A Khan 2 1 Department of Veterinary Biomedical Sciences, PMAS-Arid Agriculture University Rawalpindi, 46300, Shamasabad square, Pakistan 2 Department of Veterinary Pathobiology, PMAS-Arid Agriculture University Rawalpindi, 46300, Shamasabad square, Pakistan Abstract Pregnancy and postpartum changes affect more than a half of women in the world. Neuroactive steroids play a vital role in mental health, behavior, mood development, neuron-protection and memory. This review sums up what is well- known regarding the two types of neuroactive steroids viz. allopregnanolone (ALP) and tetrahydrodeoxycorticosterone (THDOC). There is a strong correlation between body progesterone concentration and ALP production. The stage of estrus cycles determines the levels of ALP in body, however, THDOC is a stress induced neuroactive steroid and its level is changeable with the type and severity of stress. The physiological response of stress is affected by THDOC and infuences paraventricular nucleus in hypothalamus which in turn controls hypothalamic-pituitary-adrenal and gonadal axis. Both neuroactive steroids are potent endogenous modulators of γ-aminobutyric acid type A (GABA A ) receptors and their production gets higher during pregnancy. Now a question arises “do both classes of neuroactive steroids have a potent correlation in their action?” This manuscript will bring you up to date on the interaction and function of these two during pregnancy and postpartum depression. Journal of Steroids & Hormonal Science J o u r n a l o f S t er o i d s & H o r m o n a l S c i e n c e ISSN: 2157-7536