Rodent Models of Non-classical Progesterone Action Regulating Ovulation.

Melinda A Mittelman-Smith,Margaret A Mohr,Paul E Micevych,Lauren M Rudolph

doi:10.3389/fendo.2017.00165

Melinda A Mittelman-Smith, Margaret A Mohr + Show 2 more

Open Access

https://doi.org/10.3389/fendo.2017.00165

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Abstract

It is becoming clear that steroid hormones act not only by binding to nuclear receptors that associate with specific response elements in the nucleus but also by binding to receptors on the cell membrane. In this newly discovered manner, steroid hormones can initiate intracellular signaling cascades which elicit rapid effects such as release of internal calcium stores and activation of kinases. We have learned much about the translocation and signaling of steroid hormone receptors from investigations into estrogen receptor α, which can be trafficked to, and signal from, the cell membrane. It is now clear that progesterone (P4) can also elicit effects that cannot be exclusively explained by transcriptional changes. Similar to E2 and its receptors, P4 can initiate signaling at the cell membrane, both through progesterone receptor and via a host of newly discovered membrane receptors (e.g., membrane progesterone receptors, progesterone receptor membrane components). This review discusses the parallels between neurotransmitter-like E2 action and the more recently investigated non-classical P4 signaling, in the context of reproductive behaviors in the rodent.

Highlights

We understood that steroids functioned as ligand-gated transcription factors that enacted changes in gene expression [1]
PGRMC1 promotes the activity of aromatase, an enzyme crucial for estrogen synthesis [65]. These interactions with P450 enzymes suggest a role for PGRMC1 in steroid synthesis, and perhaps PGRMC1 is involved in neural synthesis of steroid hormones
Further experiments are needed to determine if newly born astrocytes in the hypothalamus are the source of neuroP that is critical for the luteinizing hormone (LH) surge

Summary

INTRODUCTION

We understood that steroids functioned as ligand-gated transcription factors that enacted changes in gene expression [1]. This review will discuss the hallmarks of non-classical E2 signaling alongside the growing literature of membrane-initiated P4 signaling, and how neurotransmitter-like effects of these steroid hormones function, often interdependently, to direct the structure and function of neuroendocrine systems critical for reproduction. With a short exposure to E2, mu-opioid receptors are activated and internalized, a step critical for the subsequent, delayed expression of sexual receptivity [15] This effect can be elicited within minutes by cell-impermeable E-6-BSA (E2 conjugated to bovine serum albumin), demonstrating that these E2 actions are both rapid and membrane-initiated [16]. While the specific roles of non-classical PGRs in LH release are unknown, their neuroanatomical locations and their functions in non-neural reproductive tissues supports the idea that these receptors can mediate rapid, membrane-initiated P4 signaling. These interactions with P450 enzymes suggest a role for PGRMC1 in steroid synthesis, and perhaps PGRMC1 is involved in neural synthesis of steroid hormones

Neural Synthesis of Steroids

Lordosis Behavior

Findings

CONCLUSION