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ABSTRACT: The estrogen induction of progesterone receptors (PRs) in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is critical for the regulation of female sexual behavior. VMNvl neurons express PRs and both types of estrogen receptors (ERα and ERβ), and their sequential activation initiates the molecular mechanisms underlying sexual behavior. To assess the relative importance of each ER subtype in the induction of PRs, we have estimated the total number of PR-immunoreactive neurons and quantified the total amount of PR protein in the VMNvl of adult ovariectomized rats that were injected with either estradiol benzoate (EB) or the specific agonists of the ERα, propyl-pyrazole triol (PPT), and of the ERβ, diaryl-propionitrile (DPN), in different doses and schedules. The administration of EB and of PPT alone, but not of DPN alone, increased the total number of PR-immunoreactive neurons and PR protein levels. When the specific agonists were administered sequentially, the total number of PR-immunoreactive neurons also increased, particularly when PPT was administered before DPN. Conversely, the concomitant administration of PPT and DPN did not increase the number of PR-immunoreactive neurons. The observation that PPT increases the number of PR-immunoreactive neurons and the levels of PR protein far less than EB shows that the estradiol induction of PRs in the VMNvl does not involve solely the activation of the ERα and suggests that it might also implicate the activation of membrane receptors. The present results also show that ERβ activation averts the action of ERα in the induction of PRs.
Neuroscience 02/2013; · 3.38 Impact Factor
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ABSTRACT: The ventromedial nucleus of the hypothalamus is well known for its involvement in the regulation of the female reproductive behavior. The dendritic trees of neurons in its ventrolateral division (VMNvl), the dendritic spines, and the dendritic and spine synapses undergo alterations along the estrous cycle. Because these changes are conspicuous, we thought of interest to examine the influence of sex steroids in the levels of the structural proteins of axons and dendrites. The VMNvl of female rats at all phases of the estrous cycle was labeled for growth-associated protein-43, microtubule-associated protein 2, synapsin 1 and actin. The intensity of the labeling was measured using a modified Brightness-Area-Product method that is sensitive to variations the size of the VMN. The brightness per unit area of these proteins did not undergo significant variations over the estrous cycle, except synapsin 1 that was significantly reduced in diestrus relative to the remaining phases of the ovarian cycle. Conversely, the Brightness-Area-Product of all labeled proteins changed along the estrous cycle and was greater at proestrus than at all other phases. Our results show the presence of estrous cycle-related oscillations in the levels of the structural proteins that are involved in dendritic and synaptic plasticity.
Journal of Molecular Neuroscience 09/2011; 46(3):622-30. · 2.50 Impact Factor
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ABSTRACT: The effects of estrogens on the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) are essential for its role in the regulation of female sexual behavior. Enhanced synaptogenesis and induction of progesterone receptors (PRs) are hallmarks of the actions of estrogens on the VMNvl. To investigate the influence of neural afferents in mediating these effects, we estimated the number of spine and dendritic synapses per neuron and the total number of PR-immunoreactive neurons in ovariectomized rats treated with either estradiol benzoate or vehicle, after unilateral VMN deafferentation. The estimates were performed independently in the VMNvl of the deafferented and contralateral sides, and in the VMNvl of unoperated rats (controls). The administration of estradiol benzoate did not induce any increase in the number of synapses of the deafferented VMNvl. In the contralateral VMNvl, the synaptogenic effects of estrogen were apparent, but still reduced relative to the control VMNvl, where a 25% increase in the total number of synapses was observed after estrogenic stimulation. In the absence of estrogenic stimulation, i.e., in basal conditions, deafferentation reduced the number of dendritic and spine synapses, but particularly the latter. The reduction was also visible, but less marked, in the contralateral VMNvl. Contrary to synapses, the estrogen induction of PRs was unaffected by deafferentation, and the total number of PR-immunoreactive neurons was similar in the control, deafferented and contralateral VMNvl. The results show that estrogens enhance synaptogenesis in the VMNvl by acting through neural afferents and induce PR expression by acting directly upon VMN neurons.
Brain research 10/2010; 1366:60-70. · 2.46 Impact Factor
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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 approximately 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 (approximately 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.
The Journal of Comparative Neurology 04/2005; 484(1):68-79. · 3.81 Impact Factor
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ABSTRACT: In mammals, the main circadian pacemaker is located in the suprachiasmatic nucleus (SCN) and its most potent synchronizer is the daily variation of the intensity of light. However, other nonphotic cues, such as timed food restriction, can induce changes in the circadian rhythms, leading also to the appearance of a food-entrained oscillator. The present study was designed to establish if the alterations of the circadian rhythms induced by timed hypocaloric food restriction are accompanied by structural changes in the SCN. Two groups of adult rats, both maintained on 12-h light/12-h dark cycles, were used; in one group, animals had permanent free access to food, whereas in the other they were subjected to a restricted hypocaloric early morning feeding during 7 months. Using stereological techniques and in situ hybridization, we have examined the structure of the SCN and the synthesis and expression of vasopressin (AVP) and vasoactive intestinal peptide (VIP). The volume of the SCN and the total number of neurons did not vary between the two groups. However, the total number of AVP- and VIP-immunoreactive neurons and the AVP and VIP mRNA levels were significantly decreased in timed hypocaloric food-restricted animals. The results indicate that timed hypocaloric food restriction has led to changes of AVP and VIP content of the neurons. They furthermore suggest the existence of a coupling between the food-entrainable oscillator and the light-entrainable pacemaker.
Brain Research 11/2004; 1022(1-2):226-33. · 2.73 Impact Factor
