Shailaja K Mani, Ph.D.
Departments of Molecular and Cellular Biology and Psychiatry and Behavioral Sciences
Ph.D: Nagpur University, India
Postdoctoral training: Baylor College of Medicine, Houston
Molecular Mechanisms of Steroid Hormone Action in Brain Function
The long-term goal of my research is to understand the molecular and cellular mechanisms of steroid hormone action in the brain that regulate physiology and behavior. Current studies in my laboratory are examining the molecular regulation of progestin receptor (PR) in the brain to understand how the activated genes and genomic networks alter the physiological state of the neurons to activate behavior.
We have identified three distinct mechanisms by which neuronal PRs are regulated in the central nervous system (CNS).
- We have demonstrated that Progesterone effects are primarily mediated by its interaction with nuclear PRs.
- In addition to its function as a progesterone-dependent nuclear transcription factor regulating gene expression in the CNS, PRs could also be activated in a "ligand-independent" manner by certain neurotransmitters like dopamine to regulate reproductive physiology and behavior. We demonstrated the existence of cross talk between the progesterone- and dopamine-initiated signaling pathways and highlighted the critical role of DARPP-32 in the integration of these pathways.
- Furthermore, recent studies from the laboratory have also identified the involvement of cytosolic pathways mediating the rapid non-classical effects of progesterone in the activation of PRs.
We are currently exploring the cross-talk mechanisms by which these pathways converge and activate the classical intracellular receptor-dependent pathways at transcriptional and post-transcriptional levels in the CNS using a variety of molecular, cellular, biochemical and behavioral approaches. The studies will provide a molecular framework for the regulatory mechanisms by which neuronal PRs in the CNS integrate signals from multiple stimuli to control gene regulation and biological function.
A second research interest of the laboratory is to understand the neurobiological mechanisms that underlie the sex differences in the function of the adult hypothalamo-pituitary-adrenal (HPA) axis. Sex differences in the HPA axis arise as a result of the influence of gonadal steroid hormones during development and adulthood. It is well known that females exhibit a more robust activation of the HPA axis following stress than do the males. We are investigating the mechanisms by which neural estrogen receptors mediate sex differences in the HPA function. Traditional gene knockout and conditional mutant mice are currently used in these studies.
Baylor College of Medicine
One Baylor Plaza, Taub Research Building T721
Houston, TX 77030
- Mani S, Portillo W. (2010). Activation of progestin receptors in female reproductive behavior: Interactions with Neurotransmitters. Frontiers in Neuroendocrinology. 31: 157-171.
- Balasubramanian B and Mani SK. (2009). Dopamine Agonist Signaling in the hypothalamus of female rats is independent of calcium-dependent kinases. J. Neuroendocrinology. 21: 954-960.
- Balasubramanian B, Portillo W, Reyna A, Chen JZ, Moore AN, Dash PK and Mani SK. (2008). Non-classical Mechanisms of Progesterone Action in the Brain: I. PKC Activation in the Hypothalamus of Female Rats. Endocrinology 149: 5509-5517.
- Balasubramanian B, Portillo W, Reyna A, Chen JZ, Moore AN, Dash PK, Mani SK. (2008). Non-classical Mechanisms of Progesterone Action in the Brain: II. Role of CAMK II in Progesterone-Mediated Signaling in the Hypothalamus of Female Rats. Endocrinology 149: 5518- 5526.
- Gill JC, Wadas B, Chen P, Portillo W, Reyna A, Jorgensen E, Mani S, Schwarting GA, Moente SM, Tobet S, Kaiser UB. (2008). The GnRH neuronal population is normal in size and distribution in GnRH-deficient and GnRH receptor-mutant hypogonadal mice. Endocrinology 149: 4596-4604.
- Mani S. (2008). Progestin receptor subtypes in the brain: the known and the unknown. Endocrinology, 49: 859-866.
- Mani SK, Reyna AM, Chen JZ, Mulac-Jericevic B, Conneely OM. (2006). Differential Response of Progesterone Receptor Isoforms in Hormone-dependent and -independent Facilitation of Female Sexual Receptivity. Mol Endocrinol. 20:1322-1332.
- Lau YE, Cherry JA, Baum MJ, Mani SK. (2003). Induction of Fos in the accessory olfactory system by male odors persists in female mice with a null mutation of the aromatase (cyp 19) gene. Brain Res. Bull. 60:143-150.
- Mani SK, Mitchell AM and O'Malley BW. (2001). Progesterone Receptor and dopamine receptors is required in the ∆9-Tetrahydrocannabinol-Modulation of Sexual Receptivity in Female Rats. Proc. Natl. Acad. Sci. USA, 98: 1249-1254.
- Mani SK, Fienberg A, Allen P, Greengard P. et al (2000). Requirement for DARPP-32 in progesterone-facilitated sexual receptivity in female rats and mice. Science, 287:1053- 1056.