Susana Isabel Ferreira da Silva de Sá ESTROGÉNIOS E ...

Estrogen Modulates the Sexually
Dimorphic Synaptic Connectivity of the
Ventromedial Nucleus
SUSANA I. SÁ AND M. DULCE MADEIRA*
Department of Anatomy, Porto Medical School, 4200-319 Porto, Portugal
ABSTRACT
Neurons in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl)
display a remarkable estrogen-dependent functional and structural plasticity, which is likely
to be mediated, in part at least, by neuronal afferents. The present study was designed to
determine whether the number of synapses per neuron and the size of individual synapses in
the VMNvl vary across the estrus cycle and, also, whether they differ between the sexes. To
accomplish this, the VMNvl of adult female rats at proestrus or diestrus day 1 and of
age-matched male rats was analyzed using electron microscopy. We found that a single
VMNvl neuron receives around 7,000 synapses during diestrus and 10,000 during
proestrus. This estrus cycle-related variation is accounted for by increases in the number of
all types of synapses. In males, the number of synapses received by each VMNvl neuron is
similar to that of diestrus rats (7,500). However, in males the number of axodendritic and
axospinous synapses is smaller than in proestrus rats, whereas the number of axosomatic
synapses is higher than in diestrus rats. In addition, we found that the size of the postsynaptic
densities of axospinous and axosomatic synapses is consistently larger in males than in
females. Our results show that the synaptic organization of the VMNvl is sexually dimorphic,
with females having more dendritic synapses and males more somatic synapses. They also
show that the synaptic plasticity induced by estrogen in the VMNvl is characterized by
changes in the number, but not the size, of the synapses. J. Comp. Neurol. 484:68–79, 2005.
© 2005 Wiley-Liss, Inc.
Indexing terms: VMN; synaptic plasticity; sex differences; estrus cycle; stereology; hypothalamus
The ventromedial nucleus (VMN) of the hypothalamus
is a key region in the regulation of the hormone-dependent
expression of the lordosis reflex, the sexual response in
female rodents. This functional attribute has been mainly
ascribed to its ventrolateral division (VMNvl), a major
target for gonadal steroids (Pfaff and Keiner, 1973; Simerly
et al., 1990; Shughrue et al., 1997) that has strong
connections with other limbic-hypothalamic nuclei containing
estrogen-sensitive neurons (for reviews, see Madeira
and Lieberman, 1995; Simerly, 2002; see also Canteras
et al., 1994). One particularly interesting feature of
the VMNvl is that its neurons display a remarkable
estrogen-dependent functional and structural plasticity.
Estrogen implants in the VMNvl restore lordosis behavior
in female rats made nonreceptive by ovariectomy (Rubin
and Barfield, 1980) and estrogen treatment of ovariectomized
rats increases the size of neuronal cell bodies and
organelles involved in protein synthesis (Cohen and Pfaff,
1981; Carrer and Aoki, 1982; Cohen et al., 1984; Jones et
al., 1985), the number of dendritic spines (Frankfurt and
© 2005 WILEY-LISS, INC.
THE JOURNAL OF COMPARATIVE NEUROLOGY 484:68–79 (2005)
McEwen, 1991a; McEwen and Wooley, 1994; Calizo and
Flanagan-Cato, 2000), and the density of terminals (Carrer
and Aoki, 1982) and synapses (Carrer and Aoki, 1982;
Nishizuka and Pfaff, 1989; Frankfurt and McEwen,
1991b; McEwen and Wooley, 1994).
There is also evidence that, during the female reproductive
cycle, physiological levels of gonadal steroids influence
the morphology of VMNvl neurons. Neuronal cell
bodies enlarge (Madeira et al., 2001), dendrites elongate
(Madeira et al., 2001), and dendritic spines increase in
Grant sponsor: Fundação para a Ciência e a Tecnologia (FCT); Grant
number: Project POCTI/NSE/42834/2001; Grant number: Unit 121/94.
*Correspondence to: M. Dulce Madeira, Department of Anatomy, Porto
Medical School, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
E-mail: madeira@med.up.pt
Received 2 August 2004; Revised 6 September 2004; Accepted 16 November
2004
DOI 10.1002/cne.20451
Published online in Wiley InterScience (www.interscience.wiley.com).
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