Rapid Control of Reproductive Behaviour by Locally Synthesised Oestrogens: Focus on Aromatase

Abstract

Oestrogens activate nucleus-and membrane-initiated signalling. Nucleus-initiated events control a wide array of physiological and behavioural responses. These effects generally take place within relatively long periods of time (several hours to days). By contrast, membrane-initiated signalling affects a multitude of cellular functions in a much shorter timeframe (seconds to minutes). However, much less is known about their functional significance. Furthermore, the origin of the oestrogens able to trigger these acute effects is rarely examined. Finally, these two distinct types of oestrogenic actions have often been studied independently such that we do not exactly know how they cooperate to control the same response. The present review presents a synthesis of recent work carried out in our laboratory that aimed to address these issues in the context of the study of male sexual behaviour in Japanese quail, which is a considered as a suitable species for tackling these issues. The first section presents data indicating that 17b-oestradiol, or its membrane impermeable analogues, acutely enhances measures of male sexual motivation but does not affect copulatory behaviour. These effects depend on the activation of membrane-initiated events and local oestrogen production. The second part of this review discusses the regulation of brain oestrogen synthesis through post-translational modifications of the enzyme aromatase. Initially discovered in vitro, these rapid and reversible enzymatic modulations occur in vivo following variations in the social and environment context and therefore provide a mechanism of acute regulation of local oestrogen provision with a spatial and time resolution compatible with the rapid effects observed on male sexual behaviour. Finally, we discuss how these distinct modes of oestrogenic action (membrane-versus nucleus-initiated) acting in different time frames (short-versus long-term) interact to control different components (motivation versus performance) of the same behavioural response and improve reproductive fitness.

Male fidelity expressed through rapid testosterone suppression of ultrasonic vocalizations to novel females in the monogamous California mouse

“…The precise mechanism through which T is acting cannot be determined in the present study, but recent research has identified intriguing rapid effects of steroid hormones achieved by non-genomic mechanisms (Cornil et al, 2013;Mangiamele and Thompson, 2012), including effects on acoustic communication (RemageHealey and Bass, 2010;Remage-Healey and Joshi, 2012). Aromatase conversion of the precursor T to estradiol has been identified as a key process in rapid modulation of vocal behavior (Schlinger et al, 1999), which is interesting considering that aromatase expression in the medial preoptic area (mPOA), a nucleus with known involvement in both sexual and parental behavior (Dominguez and Hull, 2005;Kentner et al, 2010), increases in response to fatherhood in male California mice (Trainor et al, 2003).…”

In vivo visualization of aromatase in animals and humans

“…While it is true that no estrogen is produced in the absence of aromatase, changes in enzyme activity can result in increases or decreases in tissue estrogen levels with no change in aromatase expression. In fact, such changes have been shown to occur relatively quickly and appear to account for at least some behaviors related to estrogen in the brain of animals (Cornil et al, 2013, Dickens et al, 2014). To gain a complete picture of normal and abnormal changes in regional estrogen synthesis capacity, it would be advantageous to develop radiotracers which are substrates rather than non-competitive inhibitors of the enzyme.…”

Brain estrogen production and the encoding of recent experience

“…Brain-derived steroids provide a local source of neuromodulators that can act upon neural circuits at rapid timescales akin to classical neurotransmitters (seconds to minutes) [2]. While the rapid effects of steroid hormones are often studied in the context of sexual behavior [3], the role of neurosteroids in behaviors and neural systems beyond reproduction has only recently received attention. One area in particular has been understanding how estrogen signaling may enhance or otherwise alter cognition on momentary timescales.…”

“…Therefore it is important to clarify the functional role of reduced neural E2 production in the acquisition of sensory experience, in songbirds, rats and other model systems. In particular, key future research directions include understanding the acute control mechanisms for in vivo brain aromatase activity (such as calcium-dependent phosphorylation of the enzyme [3]), as well as improving our temporal resolution for the fluctuations in neuroestradiol during and following discrete learning events.…”