Oestrogen Regulation of Sexual Behaviour, Mood and Cognition

Osborne FX Almeida, University of Minho, Braga, Portugal
Gillian L Condé, University of Wolverhampton, Wolverhampton, UK
Nuno Sousa, University of Minho, Braga, Portugal

Published online: January 2013

DOI: 10.1002/9780470015902.a0000101.pub3

Oestrogens are steroid hormones that act through specific receptors in the brain to influence sexual behaviour, as well as mood and cognition. Oestrogen actions include alterations of neuronal excitability, neurotransmitter synthesis and metabolism, neuronal circuitry and neuronal survival, one or all of which may contribute to their effects on mood and cognition. Oestrogens act on a wide variety of peripheral tissues such as breast, bone, liver and heart tissues. Although they have found widespread use for the management of menopausal symptoms, the current consensus is that oestrogen replacement therapy should be used at the lowest possible doses, for a limited duration and with careful consideration of the individual woman's treatment goals and risks. Oestrogens regulate gene transcription, resulting in long-lasting biochemical changes that can impact adversely on health. The development of improved selective oestrogen receptor modulators that target specific tissues may eventually help circumvent some of the undesired effects of oestrogens.

Key Concepts:

  • Oestrogens serve important physiological roles in the brain and in peripheral organ systems.
  • Oestrogens and oestrogen-like compounds bind to oestrogen receptors; oestrogen receptors occur as two isoforms, known as oestrogen receptor, ER and ER
  • Oestrogens modulate gene activity, cellular structure and function and ultimately, regulate complex behaviours after binding to specific oestrogen receptors in the brain.
  • Oestrogen secretion starts during early development, varies cyclically from puberty onwards, and gradually diminishes with age (menopause in women).
  • Oestrogen-like compounds that raise health issues are increasingly found in our modern environment as well as in plants; the potency and safety of the latter, especially as dietary supplements, is however questionable.
  • The therapeutic use of oestrogens in menopausal women should be tailored to an individual woman's needs and should be limited in order to avoid health-related reductions in quality of life.

Keywords: sexual differentiation; sexual behaviour; mood; cognition; endocrine disruptor compounds; hormone replacement therapy; oestrogen receptor; neuron

Figure 1. Structural formulae of the naturally occurring gonadal steroids: (a) testosterone, (b) 17-oestradiol, which is derived from testosterone through the action of the enzyme aromatase and (c) equilenin. Structure of the ‘steroid backbone’, labelled according to convention, is shown in the top left-hand corner of the illustration. Three representative members of the phyto-oestrogen family, coumestrol, genistein and resveratrol, are shown in (d–f); these plant-derived oestrogens display weak potencies at the oestrogen receptor. The chemical formula of diethylstilboestrol, a highly potent synthetic nonsteroidal oestrogen, is depicted in (g); DES was originally used to prevent spontaneous abortions, but it is no longer used as a therapeutic agent because of its highly carcinogenic nature. The structures of two common nonsteroidal ‘endocrine disrupter compounds’, bisphenol A and DDT, are represented in (h) and (i), respectively; the use of EDCs is now prohibited in most countries. Tamoxifen (j), ICI 182780 (k) and raloxifene (l) serve as examples of nonsteroidal ‘designer oestrogens’ or ‘selective oestrogen receptor modulators’. Tamoxifen is used for the treatment of oestrogen-dependent breast cancers. ICI 182780 shows greater oestrogen receptor selectivity than tamoxifen and shows considerable potential as a therapeutic agent. Raloxifene was recently approved for use in the prevention of osteoporosis. The structure of 3Adiol is shown in (m); this compound is reportedly an endogenous oestrogen that shows higher affinity for ER than ER. The inset (top left-hand corner) shows the structure of the basic ‘steroid rings'.
Figure 2. Schematic representation of the ovarian cycle in women, based on an average cycle length of 28 days with ovulation occurring on day 14. Note that oestradiol concentrations gradually rise with increasing size of the developing ovarian follicle and reach a peak just before ovulation before declining. The secretory profile of progesterone follows that of the development of the corpus luteum; progesterone levels plummet when the corpus luteum regresses, and this is accompanied by the menstrual bleeding due to sloughing of the endometrium lining the walls of the uterus.
Figure 3. Schematic distribution of ER isoforms ( and ) in the brain, based on published maps generated by immunocytochemistry and in situ hybridisation histochemistry. The number of pluses refers to the relative abundance of each isoform. Only those areas of the brain relevant to functions discussed in this article are shown. Seversal hypothalamic nuclei express one or both ER isoforms; of particular relevance are the preoptic area, which is responsible for the control of sex steroid secretion, and the ventromedial nucleus, which is strongly implicated in the regulation of sexual behaviour.
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Related Sub-Topics:

Neurotransmitters | Receptors for Neurotransmitters | Intracellular and Extracellular Signalling
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Article Title: Oestrogen Regulation of Sexual Behaviour, Mood and Cognition
 
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Almeida, Osborne FX, Condé, Gillian L, and Sousa, Nuno(Jan 2013) Oestrogen Regulation of Sexual Behaviour, Mood and Cognition. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000101.pub3]