**6. Neuroendocrine signals**

At present there is no doubt that in addition to pituitary and non-pituiraty hormone control, ovarian functions, hormone synthesis and ovulation, as well as adrenal cortex secretions, and perhaps the secretion of hormones by the testicles and even spermatogenesis, are under direct local neural modulation.

Kawakami et al. (1979, 1981) obtained the first unequivocal results indicating that the regulation of ovarian functions is accomplished by hormonal signals that are modulated by neural signals. Applying electric stimulation to the ventromedial hypothalamus and the medio-basal prechiasmathic area in hypophysectomized and adrenalectomized rats provoked the release of progesterone and estradiol without modifying ovarian blood flow.

The synthesis and secretion of steroids from the adrenal cortex and ovaries are also under direct modulation by local neurons. Without making synaptic contact, many noradrenergic nerve endings are in close proximity to zona-glomerulosa cells. NA acts as a direct modulator of local steroid secretion. Catecholamines and adenosine triphosphate (ATP)

Protein kinases (PKs) are a group of enzymes that modify other enzymes by adding

PKs participate in regulating the release of steroid hormones. Ovarian cells produce a number of PKs whose expression depends on the type of cell, their state and the action of hormones and other PKs (Sirotkin et al., 2011). In mammalian ovarian cells, PK-A stimulates the release of progesterone and estradiol (Makarevich et al., 2004); while others affirm that PKA inhibits progesterone, testosterone and estradiol release by mammalian ovarian follicular cells (Dupont et al., 2008). In chickens, PK-A either stimulates or suppresses the release of progesterone, testosterone and estradiol (Sirotkin & Grossmann, 2006, 2007b). In corpus luteum, PK-A promotes the release of progesterone by large luteal cells, while PK-C inhibits the release of progesterone and maintains luteal prostaglandin 2 alpha release (Diaz et al., 2002; Niswender, 2002). According to Makarevich (2004) PK-A type II is more

Rabbit ovaries treated *in vitro* with dbcAMP secrete less progesterone and testosterone, but basal estradiol release remained unchanged. Adding FSH, IGF-I, and ghrelin reduced progesterone release, and adding only ghrelin increased the release of testosterone without modifying estradiol output. Previous treatment with dbcAMP inverted the inhibitory to stimulatory action of FSH, IGF-I and ghrelin on progesterone release (Chrenek et al., 2010).

Like the adrenal glands, the ovaries secrete steroid and polypeptidic hormones that regulate

Estradiol regulates the synthesis of androgens by the follicular theca interna in an inhibitory way. Estrogens and androgens inhibit progesterone secretion by the human corpus luteum. The effects of testosterone and androstenedione are mediated by their conversion to estrogens (Tropea et al., 2010). Androgens stimulate cytochrome P450 aromatase mRNA concentrations in granulosa cells. The effects depend on the androgen studied, suggesting that the expression of the aromatase gene has differential regulation in the developing follicle (Hamel et al., 2005). GnRH-like peptides in the testicle and ovary play an inhibitory

At present there is no doubt that in addition to pituitary and non-pituiraty hormone control, ovarian functions, hormone synthesis and ovulation, as well as adrenal cortex secretions, and perhaps the secretion of hormones by the testicles and even spermatogenesis, are under

Kawakami et al. (1979, 1981) obtained the first unequivocal results indicating that the regulation of ovarian functions is accomplished by hormonal signals that are modulated by neural signals. Applying electric stimulation to the ventromedial hypothalamus and the medio-basal prechiasmathic area in hypophysectomized and adrenalectomized rats provoked the release of progesterone and estradiol without modifying ovarian blood flow. The synthesis and secretion of steroids from the adrenal cortex and ovaries are also under direct modulation by local neurons. Without making synaptic contact, many noradrenergic nerve endings are in close proximity to zona-glomerulosa cells. NA acts as a direct modulator of local steroid secretion. Catecholamines and adenosine triphosphate (ATP)

phosphate groups (phosphorylation), which changes the enzyme's activity.

important for the control of ovarian steroidogenesis than PK-A type I.

/modulate the synthesis and release of ovarian hormones.

regulation on steroidogenesis (Franchimont, 1983).

**6. Neuroendocrine signals** 

direct local neural modulation.

**5.7 Protein kinases and cAMP** 

**5.8 Ovarian signals** 

diffuse into zone glomerulosa cells and modulate the synthesis of aldosterone in a paracrine way. The enzymes that may terminate the effect of ATP are present in the nerve endings, suggesting that ATP and its metabolites influence the production of aldosterone. Thus, catecholamines and ATP play a paracrine non-synaptic modulator role of in the regulation of adrenocortical steroid secretion (Szalay et al., 1998).

Stimulation of beta-adrenoreceptors, VIP receptors or the forskolin-induced activation of cAMP formation of 2-day-old rat ovaries increases the steady state levels of the mRNAs encoding P-450aromatase and FSH receptors. Based on these results it was suggested that ovarian nerves, acting via neurotransmitters coupled to the cAMP generating system, contribute to the differentiation process by which newly formed primary follicles acquire FSH receptors and responsiveness to FSH. Follicles that grow in more densely innervated ovarian regions may have a selective advantage over those not exposed to neurotransmitteractivated, cAMP-dependent signals; and thus may become more rapidly subjected to gonadotropin control (Mayerhofer et al., 1997).

The intra-cerebro-ventricular injection (icv-i) of isoproterenol (beta-adrenergic agonist) to rats in diestrus 2 lowers progesterone levels in the ovarian vein blood. However, no apparent effects are observed when both superior ovarian nerves (SON) are sectioned before the icv-i treatment. Blocking the beta-adrenergic receptors with propranolol icv-i increased progesterone levels, an effect that was not observed when both SONs were sectioned (De Bortoli et al., 1998, 2002). According to De Bortoli et al. (2000), the neural signals arriving to the ovary through the SON antagonize the ovarian LH regulation of progesterone and androstenedione.
