**7. Ovarian and adrenal innervations**

The adrenal gland and the ovaries receive innervation from several nerve fibers of extrinsic and intrinsic origin. Most of the extrinsic innervations in the adrenal derive from the sympathetic nervous system, including cholinergic fibers containing nitric oxide synthase (Holgert et al., 1995), thyrosine hydroxylase- and neuropeptide Y-positive postganglionic sympathetic fibers (Holgert et al., 1998; Kondo, 1985). Encephalin was exclusively found in choline-acethyl-transferase positive fibers among adrenaline chromaffin cells (Holgert et al., 1995). Intrinsic innervation originates from two different types of medullary ganglion cells: Type I and Type II cells. Type I cells are NPY-positive noradrenergic, while type II ganglion cells synthesize VIP and nitric oxide synthase (Holgertet al., 1998; Ulrich-Lai et. al., 2006).

The adrenals have efferent fibers connecting to the dorsal motor nucleus of the vagus nerve, while other fibers of vagal origin reach the gland via the celiac or suprarenal ganglion (Berthoud and Powley, 1993; Coupland et al., 1989). In the rat, the motor and sensory vagal innervations of the adrenal gland originate from bilaterally situated cell bodies that have slight ipsi-lateral predominance (Coupland et al., 1989). Nerve fibers that go to and from the adrenal gland also possess afferent viscero-sensory fibers. According to Tóth et al. (2007), the steroid feedback mechanism affects the cerebral structures that send descending input to the sympathetic preganglionic neurons innervating the adrenal gland.

The bilateral sectioning of the thoracic splanchnic nerve resulted in lower corticosterone plasma levels measured in the afternoon seven days after treatment, without apparent changes in ACTH levels; results that suggest that the splanchnic adrenal innervation modulates the response to ACTH. The effects are related to functional changes in the adrenal medulla and do not depend on the sensitive of the afferent fibers (Ulrich-Lai et al., 2006).

Hormonal and Neural Mechanisms Regulating Hormone Steroids Secretion 15

hormone (CRH) and by the noradrenergic system. CRH has an inhibitory modulation of testosterone, dihydro-testosterone, and androstane-3alpha, 17beta-diol secretion, while epinephrine and norepinephrine have a stimulatory effect through alpha1/beta1-adrenergic

Stress induced by sleep deprivation results in lower testosterone levels in serum and lower testicular StAR protein expression, while serotonin and corticosterone serum levels are elevated (Wu et al., 2011). These results suggest that serotonin regulation of steroid

Acting through -1 and -2 receptors, NA stimulates progesterone secretion from luteal slices of heifers, and increases cytochrome P-450scc and 3 beta-HSD activity (Miszkiel & Kotwica, 2001). Nitric oxide (NO) inhibits the activity of cytochrome P450 aromatase and the secretion of estradiol by granulosa cells in culture (Ishimaru et al., 2001). *In vitro* studies show that in the rat, the participation of neurotransmitters regulating the secretion of ovarian progesterone varies throughout the day of the estrous cycle. In diestrus-1, NPY, NA, and VIP inhibit progesterone secretion by the ovaries, while on diestrus-2 these neurotransmitters stimulate progesterone secretion. In diestrus 1 and 2, NA+VIP or NA+NPY had a synergic effect on progesterone secretion, since measured concentrations were higher than VIP or NPY treatment alone (Aguado, 2002). In the rat, ovarian denervation reduces the synthesis and secretion of progesterone by inhibiting 3-betaHSD activity (Burden & Lawrence, 1977). Sectioning the plexus nerve and the SON of pigs led to lower LH, progesterone, androstenedione (A4), testosterone, estrone and estradiol-17beta plasma levels. In addition, a significant increase in the immune-expression of cholesterol side-chain cleavage cytochrome P450 occurs in follicles, as well as a decrease in 3-betaHSD activity, and in LH, progesterone, androstenedione (A4), testosterone, estrone and estrogen

Using an *ex vivo* celiac ganglion (CG)-SON-ovary (CG-SON-O) system, Aguado's research group has contributed to the understanding of the participation of the SON, the plexus ovarian nerve and the vagus nerve in regulating the secretion of ovarian hormones. In *in vitro* studies, the release of ovarian hormones is modulated by the stimulation/inhibition of

According to Morán et al., (2005), the CG form a bilateral structure with the superior mesenteric ganglia in the rat, receiving the name of celiac-superior mesenteric ganglion (CSMG) which is composed of noradrenergic neurons called principal neurons, small

In *in vitro* studies, adding NPY, VIP or substance P (SP) to the ovaries obtained from rats in diestrus 1 resulted in lower release of progesterone, while the same treatment to ovaries obtained from rats in diestrus 2 increased it. Adding these three neuropeptides to the CG from rats in diestrus 2 resulted in higher progesterone secretion (Garraza et al., 2004). These results suggest that the way neural signals participate in the regulation of steroid secretions

Adding NA to the CG obtained from rats on diestrus 1 resulted in ovarian dopaminergic and noradrenergic activity increases, while adding NA to the CG system from rats on diestrus 2 only increased noradrenergic activity. Such changes in dopaminergic and noradrenergic ovarian activities resulted in lower release of androstenedione in systems obtained from rats on diestrus 1, and higher release of androstenedione in systems obtained

depends on the day of the estrous cycle and the type of cells receiving the signal.

hormones release depends on the cells where such sterols originate.

receptors (Frungeri et al., 2002).

plasma levels (Jana et al., 2007).

neurons present in the CG.

intensely fluorescent cells, and peptidergic interneurons.

from rats on diestrus 2 (Bronzi et al., 2011).

The ovaries receive motor innervations from the sympathetic and the parasympathetic system via the vagus nerve, and possess afferent fibers travelling sympathetic and vagal routes (Burden et al 1983; Klein and Burden, 1988, Gerendai et al., 2000, 2009). The vagus nerve connects the ovaries with the area postrema, the nucleus of the solitary tract, the dorsal vagal complex, the parapyramidal nucleus, A1, A5, and A7 -cell groups, the caudal raphe nuclei, the hypothalamic paraventricular nucleus, the lateral hypothalamus, the Barrington's nucleus, the locus coeruleus, the periaqueductal gray, and the dorsal hypothalamus. All of these areas form a neural circuit that directly participates in the neural communication between the CNS and the ovaries (Gerendai et al., 2000; Tóth et al., 2007).

As in the adrenals, the ovaries have micro-ganglia with tyrosine hidroxilase positive neurons (D'Albora & Barcia, 1996; Dees et al., 1995; D'Albora et al., 2002), and along some capillaries there are neurons resting on the basal (D'Albora & Barcia, 1996).
