Hormonal symphony: steroid orchestration of gene modules for sociosexual behaviors

Abstract

Genes induced by estrogens in the mammalian forebrain influence a variety of neural functions. Among them, reproductive behavior mechanisms are very well understood. Their functional genomics provide a theoretical paradigm for linking genes to neural circuits to behavior. We propose that estrogen-induced genes are organized in modules: Growth of hypothalamic neurons; Amplification of the estrogen effect by progesterone; Preparative behaviors; Permissive actions on sex behavior circuitry; and Synchronization of mating behavior with ovulation. These modules may represent mechanistic routes for CNS management of successful reproduction. Moreover, new microarray results add estrogen-dependent genes, including some expressed in glia, suggesting possible hormone-dependent neuronal/ glial coordination. Molecular Psychiatry (2004) 9, 550-556. doi:10.1038/sj.mp.4001493Keywords: sex; estrogen; gene; hypothalamus; lordosis; arousal; noradrenalin; acetylcholine; oxytocin; enkephalin; opioid; GnRH; LHRH; neurotrophic; anxiety Sexual behaviors are important for psychiatry. Not only hypersexual disorders but also concerns about lack of sexual desire are prominent, internationally, in the psychiatric landscape. Further, in some traditions of psychiatric theory, sexual problems are held to be at the root of apparently unrelated syndromes. Finally, biological thought has held that sexual affiliations provide the bauplan, the structural precedent, for a wide variety of other social relations, both normal or abnormal. Fortunately, the molecular analysis of stereotyped sexual behaviors has benefited greatly from several strategic advantages: Even in mammals, simple stimuli and responses permit neural net analysis. Steroid hormones acting through nuclear receptors which are transcription factors invoke regulated gene expression, for example, in hypothalamic neurons.1 In turn, these neurons control mating behavior circuits.Drawing hormone-regulated gene expression into the explanation of mammalian sex behavior has proceeded rapidly. Here we theoretically propose a gene network-really, a micronet-downstream of estrogen action in the forebrain responsible for courtship and lordosis behavior in females. Not a massive review of the literature or an original data report, this paper comprises an attempt to draw different transcriptional systems into a new theoretical formulation. These efforts to explain hormone-driven behaviors have benefited from Rosenfeld's example of genetic network control over pituitary gland development.2 Both direct and indirect causal routes are depicted below.Causal routes, downstream from genomic action; a modular system emergent The primary sex behavior of female quadrupeds, lordosis, depends on defined physical signals: cutaneous stimuli and estrogens þ progestins 1 (E þ P). The neural circuit has been worked out; estrogen-dependent transcription in ventromedial hypothalamic cells allows permissive signals to the midbrain central gray, thus enabling the rest of the circuit. In the absence of fear or anxiety-pro...

Photoperiod reverses the effects of estrogens on male aggression via genomic and nongenomic pathways

“…Previous studies on estrogendependent behavior have identified promising candidate genes. For example, estrogenic regulation of oxytocin signaling is thought to mediate the effects of estrogens on social recognition (44), which could affect aggressive behavior (45). Application of ChIP to identify genes bound by ER␣ in Peromyscus brain samples could be an effective systematic approach to identifying additional pathways that are not yet implicated in the control of social behaviors.…”

Central genomic regulation of the expression of oestrous behaviour in dairy cows: a review

“…Primarily on the basis of the results of research by Pfaff and co-workers on lordosis behaviour in rodents, it has been proposed that oestradiol-activated genes in the VMH are organized in five modules referred to as GAPPS modules (Mong and Pfaff, 2004;Pfaff, 2005).…”

“…The increased synthesis of ribosomal RNA in the ventromedial hypothalamus has been reported to be one of the early effects of oestrogen administered subcutaneously in ovariectomized rats and represents a primary event in the activation of neuronal cells and neuronal pathways involved in female reproductive behaviour (Jones et al, 1990). Oestrogen-driven expansion of dendrites and synapses follows from the stimulation of synthesis of ribosomal RNA (Mong and Pfaff, 2004;Pfaff, 2005).…”

“…Oxytocin, produced by the supraoptic and paraventricular nuclei of the hypothalamus, is released within the brain where it acts on specific oxytocin receptors to elicit effects such as female sexual receptivity, grooming behaviour and partner bonding (Leng et al, 2008). In the presence of oestrogen, oxytocin exerts an anxiolytic effect, mediated by increases in oxytocin-binding density in the lateral septum, thereby favouring courtship and mating (McCarthy et al, 1997;Mong and Pfaff, 2004). Similar to oxytocin, vasopressin is associated with sexual behaviour and bonding and its expression is under the control of oestrogen and progesterone (Patisaul et al, 2003;Kalamatianos et al, 2004;Curley and Keverne, 2005;Donaldson and Young, 2008).…”

“…Furthermore, the perception and awareness of male-related cues differ with the stage of oestrous cycle, with releases of monoamines (linked to serotonin (HTR2A) and DRD2) and γ-aminobutyric acid (GABA) (linked to GABRA6) in the mediobasal hypothalamus being triggered by such cues only when ewes are in oestrus (Fabre-Nys et al, 1997). Studies on female rats and Table 3 Oestrous behaviour-associated genes and processes in dairy cows grouped in the GAPPS modules described for female sexual behaviour in rodents (Mong and Pfaff, 2004) …”