**13. References**

24 Steroids – Basic Science

Some of the effects of unilateral adrenalectomy seem to be related to the SON ovarian innervation since the unilateral section of the SON modified some of the changes in testosterone and estradiol serum levels induced by unilateral adrenalectomy. Thus, the extirpation of one adrenal could modify the activity of the neurons in the CSMG originating

The supra-spinal innervations of the adrenals and ovaries show left side predominance, and some neurons exclusively innervate a given organ (Gerendai et al., 2009). Each adrenal gland is innervated both by side-specific neurons and by neurons that project to both organs (Tóth et al., 2007). The left and right ovaries have different abilities to spontaneously release oocytes. Such differences appear to be related to the ovarian innervations, and the left ovary appears to be more competent to spontaneously release

According to Klein and Burden (1988), the number of neural fibers received by the right ovary is higher than in the left; while Toth et al., (2007) showed that the left ovary sends more neural information to the CNS than the right ovary. The right and left ovaries show different ovulatory responses to surgical denervation, and these responses vary according to the day of the estrous cycle when surgery is performed (Chávez et al., 1987, 1989; Chávez & Domínguez, 1994). These results suggest that the endocrine performances by the ovaries and adrenals present asymmetries, which are related to the innervations

Taken together the results obtained by different experimental approaches show that the synthesis and release of hormone by the adrenals and ovaries are under multiple controls. The hormonal signals arise from different sources, including the adrenals and ovaries. The adrenal and ovarian innervations modulate the effects of the hormonal signals, possibly by differences in the frequency and amplitude release of different

Because the mechanisms regulating the release of steroid hormones changes during the estrous cycle and throughout the day, it is possible that circadian signals arising from the suprachiasmatic nucleus exert a fine modulation of adrenal and ovarian cells to hormone

Currently we do not have a clear hypothesis to explain why the organs secreting steroid hormones are asymmetric, or why such asymmetry varies during the estrous cycle and the

1. Is the expression of hormones and/or neurotransmitters receptors secreted by endocrine cells under the control of proteins synthesized under the directions of the

2. Do the release characteristics (frequency and amplitude) of neurotransmitters by the axons arriving to the endocrine cells vary during the day, and do they present

3. What are the functions of the micro-ganglia in the adrenals, testicles and ovaries?

hour of the day. Questions arising in the intent to present a hypothesis include:

SON fibers.

**10. Ovarian and adrenal asymmetries** 

oocytes (Domínguez et al., 1989).

received by the organs.

**11. Conclusions** 

neurotransmitters.

and neural signals (Buijs et al.,2006).

clock genes present in the cells?

differences between one organ and the other?


Hormonal and Neural Mechanisms Regulating Hormone Steroids Secretion 27

Chung. S., Son, G.H., & Kim, K. (2011). Circadian rhythm of adrenal glucocorticoid: its

Coupland, R. E., Parker, T. L., Kesse, W. K. & Mohamed, A. A. (1989). The innervation of the

Cruz, M. E., Flores, A., Palafox, M. T., Meléndez, G., Rodríguez, J. O., Chavira, R. &

Czajka-Oraniec, I. & Simpson, E. R. (2010). Aromatase research and its clinical significance. *Endokrynolia Polska*, Vol.61 , No.1, (February 2010), pp. 126-34, ISSN 0423-104X. D'Albora, H. & Barcia, J. J. (1996). Intrinsic neuronal cell bodies in the rat ovary. *Neurosciense* 

D'Albora, H., Anesetti, G., Lombide, P., Dees, W.L. & Ojeda, S.R.(2002). Intrinsic neurons in

De Bortoli, M.A., Garraza, M.H., &Aguado, L. I. (1998). Adrenergic intracerebroventricular

De Bortoli, M. A, Garraza, M. H., & Aguado, LI. (2000). Epinephrine intracerebroventricular

De Bortoli, M. A., Garraza, M. H., &Aguado, L. I. (2002). Involvement of beta-adrenoceptors

Dees WL, Hiney JK, Schultea TD, Mayerhofer A, Danilchik M, Dissen GA, Ojeda SR. (1995).

Delarue, C., Conlon, J. M., Remy-Jouet, I., Fournier, A., & Vaudry, H. (2004). Endothelins as

Diaz, F.J., Anderson, L.E., Wu, Y. L., Rabot, A., Tsai, S. J. & Wiltbank, M. C.(2002).

2010), pp. 202-205, ISSN 0014-2999.

(May), pp. 581-591. ISSN 0006-3002.

(May 1988), pp. 2090-2097, ISSN 0013-7227.

(October 1998), pp. 61-68, ISSN 0022-0795.

(September 2000), pp.19-24 , ISSN 0960-0760.

(December 1995, pp. 5760-5768, ISSN 0013-7227.

No.1, (February 2004), pp. 1-7, ISSN 0952-5041.

*Letters*, Vol.205, No.1, (1996), pp. 61-67, ISSN 0304-3940.

173-181, ISSN 1469-7580.

pp. 484-489.ISSN 1097-0029.

780X.

FSH, IGF-I and ghrelin. *European Journal of Pharmacology,* Vol. 640, No.1-3, (August

regulation and clinical implications. *Biochimica et biophysica acta,*Vol.1812, No. 5,

adrenal gland. III. Vagal innervation. *Journal of Anatomy*, Vol.163 , (April 1989), pp.

Domínguez R. (2006). The role of the muscarinic system in regulating estradiol secretion varies during the estrous cycle: the hemiovariectomized rat model. *Reproductive Biology and Endocrinology*, (August 2010), pp. 4-43, ISSN 1945-7170. Cunningham, L. A. & Holzwarth, M. A. (1988). Vasoactive intestinal peptide stimulates

adrenal aldosterone and corticosterone secretion. *Endocrinology*. Vol. 122, No. 5,

the mammalian ovary. *Microscopy Research Technology*. Vol.59, No. 6 (December 15),

stimulation affects progesterone concentration in the ovarian vein of the rat: participation of the superior ovarian nerve. *Journal of Endocrinology,* Vol. 159, No.9,

stimulation modifies the LH effect on ovarian progesterone and androstenedione release. *Journal of Steroid Biochemistry & Molecular Biology*, Vol. 74, No.1-2,

in a central regulation of the ovarian progesterone release in rats. *Neuroendocrinology Letters* Vol.23 , No.3, (February 2002), pp. 27-31, ISSN 0172–

The primate ovary contains a population of catecholaminergic neuron-like cells expressing nerve growth factor receptors. *Endocrinology,* Vol. 136, No.12,

local activators of adrenocortical cells. *Journal of Molecular Endocrinology,* Vol.32,

Regulation of progesterone and prostaglandin F2alpha production in the CL. *Molecular Cell Endocrinology,* Vol. 191, No. 1 (May 2002), pp. 65-80.ISSN 1872-8057. Domínguez, R., Cruz, M. E. & Chávez, R. (1989). Differences in the ovulatory ability

between the right and left ovary are related to ovarian innervation*. In: Growth* 


Brannian, J.D., Zhao, Y., & McElroy, M. (1999). Leptin inhibits gonadotrophin-stimulated

*Reproduction,* Vol.14, No. 2 (June 1999), pp.1445-1448, ISSN 1460-2350. Bronzi, D., Orozco, A.V., Delgado, S.M., Casais, M. & Rastrilla, A.M.,& Sosa, Z.Y. (2011.)

*Sterility,* Vol. 95, No.4, ( December 2010), pp. 1211-1216, ISSN 0015-0282. Burden, H.W., Lawrence, I.E. Jr. (1977). The effects of denervation on the localization of

Buijs, R.M., Scheer, F.A., Kreier, F., Yi, C., Bos, N., Goncharuk, V.D. & Kalsbeek A. (2006)

Caminos, J. E., Nogueiras, R., Gaytán, F., Pineda, R., González, C.R., Barreiro, M.L., Castaño,

Casais, M., Delgado, S.M., Vallcaneras, S., Sosa Z., & Rastrilla, A.M. (2007). Nitric oxide in

Chávez, R., Cruz, M.E. & Domínguez, R. (1987). Differences in the ovulation rate of the right

Chávez, R., Morales, L., Gonzalez, M. E. & Domínguez, R. (1994). Ovarian norepinephrine

Chen, M. C., Wang S.W., Kan S.F., Tsai S.C., Wu Y.C. & Wang P. S. (2010) Stimulatory effects

studies. *Medical Science Research* 1994, Vol.22, (n.d.), pp.789-790, ISSN . Chávez, R., Sánchez, S., Ulloa-Aguirre, A. & Domínguez, R. (1989). Effects on estrous

Vol. 149, No. 7, (July 2008), pp. 3390-3402, ISSN 1945-7170.

No. 4 (December), pp. 623-627. 0003-276X.

ISBN 978-0-444-52261-0.

39-44, ISSN 0172-780X.

pp. 397-401, ISSN 0022-0795.

(December 1989), pp. 441-444,ISSN 0022-0795.

granulosa cell progesterone production by antagonizing insulin action. *Human* 

Modulation of the noradrenergic activity index by neural stimulus, and its participation in ovarian androstenedione release during the luteal phase. *Fertility &* 

delta5-3beta-hydroxysteroid dehydrogenase activity in the rat ovary during pregnancy. *Acta Anat (Basel).* Vol. 97, No. 3 (March), pp. 286-290. ISSN 0001-5180. Burden, H.W., Leonard,M,, Smith, C,P., Lawrence, I. E. Jr. (1983). The sensory innervation of

the ovary: a horseradish peroxidase study in the rat. *The Anatomical Record.* Vol.207,

Organization of circadian functions: interaction with the body. *Progress in Brain Research,* Vol. 153 , No., (2006), pp. 341-360. Hypothalamic Integration of Energy Metabolism, Proceedings of the 24th International Summer School of Brain Research, held at the Royal Netherlands Academy of Arts and Sciences Amsterdam, The Netherlands 29 August-01 September 2005. Edited by: A. Kalsbeek, E. Fliers, M.A. Hofman, D.F. Swaab, E.J.W. van Someren and R.M. Buijs

J.P., Malagón, M.M., Pinilla, L., Toppari, J., Diéguez, C. & Tena-Sempere, M. (2008). Novel expression and direct effects of adiponectin in the rat testis. *Endocrinology,*

prepubertal rat ovary contribution of the ganglionic nitric oxide synthase system via superior ovarian nerve. *Neuroendocrinology letters,* Vol. 28, No. 1, (February), pp.

or left ovary in unilaterally ovariectomized rats: effect of ipsi- and contralateral vagus nerves on the remaining ovary. *Journal of Endocrinology*, Vol.113, (June 1987),

content in prepubertal rats with superior ovarian nerve section. Temporally

cyclicity and ovulation of unilateral section of the vagus nerve performed on different days of the estrous cycle in the rat. *Journal of Endocrinology* ,Vol.123 , No.3,

of propylthiouracil on pregnenolone production through upregulation of steroidogenic acute regulatory protein expression in rat granulosa cells. *Toxicological Sciences*, Vol.118, No.2, (October 2010), pp. 667-74 , ISSN 1096-0929. Chrenek, P., Grossmann, R. & Sirotkin, A. V. (2010). The cAMP analogue, dbcAMP affects

release of steroid hormones by cultured rabbit ovarian cells and their response to

FSH, IGF-I and ghrelin. *European Journal of Pharmacology,* Vol. 640, No.1-3, (August 2010), pp. 202-205, ISSN 0014-2999.


Hormonal and Neural Mechanisms Regulating Hormone Steroids Secretion 29

Garraza, M. H., Aguado, L. I., & De Bortoli, M. A. (2004) In vitro effect of neuropeptides on

Gerendai, .I, Tóth, I.E., Boldogköi, Z., Medveczky, I., & Halász B. (2000) CNS structures

Ghosh, D., Griswold J, Erman M. & Pangborn W. (2009). Structural basis for androgen

Hamel, M., Vanselow, J., Nicola, E.S. & Price CA. (2005). Androstenedione increases

Hinson, J.P., Kapas, S., Orford, C.D. & Vinson, G.P. (1992). Vasoactive intestinal peptide

Holgert, H., Aman, K., Cozzari, C., Hartman, B.K., Brimijoin, S., Emson, P., Goldstein, M. &

Holgert, H., Dagerlind, A., & Hökfelt, T. (1998). Immunohistochemical characterization of

Hu, J., Zhang ,Z., Shen, W. J. Azhar, S. (2010). Cellular cholesterol delivery, intracellular

Ishimaru, R. S., Leung, K., Hong L., & LaPolt, P. S. (2001). Inhibitory effects of nitric oxide on

*Endocrinology,* Vol. 168, No.8, (February 2001), pp. 249-255, ISSN 0022-0795. Jana, B., Dzienis, A., Wojtkiewicz, J., Kaczmarek, M., & Majewski, M. (2007). Surgical

Kagerer, S. M. & Jöhren O. (2010). Interactions of orexins/hypocretins with adrenocortical

Karamouti, M, Kollia, P, Kallitsaris, A, Vamvakopoulos, N, Kollios, G, & Messinis, IE. (2009).

Nervous System. Vol. 80, No. 1-2, (April 12), pp. 40-45.ISSN 0165-1838 Gerendai, I., Tóth, I.E., Boldogkoi, Z. & Halász, B. (2009). Recent findings on the

3750.

188, ISSN 1559-0100.

( January 2009), pp. 219-223 , ISSN 0028-0836.

1992), pp.253-238,ISSN 1479-6805

1995), pp. 2576–2580, ISSN 09594965.

371, ISSN 1748-1716.

70, No. 2, (February 2005), pp.175-183. ISSN 1098-2795

Vol.30 , No.6-7, (Julio 1998), pp. 315–322, ISSN 0018-5043.

*metabolism (Lond).* Vol. 7, (June 1), p. 47, ISSN 1743-7075.

Vol.55, No.5, (M*arch* 2007), pp. 107-122 , ISSN 1588-2705.

ovary or celiac ganglion affects the release of progesterone from ovaries in the rat. *Medical Science Monitor*, Vol.10, No.12, (December 2004), pp.440-446, ISSN 1634-

presumably involved in vagal control of ovarian function. Journal of Autonomic

organization of central nervous system structures involved in the innervation of endocrine glands and other organs; observations obtained by the transneuronal viral double-labeling technique. *Endocrine*, Vol.36, No.2, (October 2009), pp. 179-

specificity and oestrogen synthesis in human aromatase. *Nature*, Vol.457 , No.7226,

cytochrome P450 aromatase messenger ribonucleic acid transcripts in nonluteinizing bovine granulosa cells. *Molecular Reproduction and Development*. Vol.

stimulation of aldosterone secretion by the rat adrenal cortex may be mediated by the local release of catecholamines. *The Journal of Endocrinology.* Vol. 133, No.2 (May

Hökfelt, T. (1995). The cholinergic innervation of the adrenal gland and its relation to enkephalin and nitric oxide synthase. *Neuroreport*, Vol.15 , No.6, (December

the peptidergic innervation of the rat adrenal gland. *Hormone Metabolic Research,*

processing and utilization for biosynthesis of steroid hormones. *Nutrition &* 

estrogen production and cAMP levels in rat granulosa cell cultures. *Journal of* 

denervation of porcine ovaries during the middle luteal phase of the oestrous cycle changes their morphology and steroidogenic activity. *Acta Veterinaria Hungarica*,

functions. *Acta Physiologica (Oxford, England),* Vol.198 , No.3, (March 2010), pp. 361-

Modulating effect of leptin on basal and follicle stimulating hormone stimulated

*Factors and the Ovary.* Editor Anne M.Hirshfield.. Chap. 39. pp.321-325. Plenum Press, New York


Domínguez, R., Morales, L. & Cruz, M.E. (2003). Ovarian asymmetry. *Annual Review of* 

Duggal, P.S., Ryan, N.K., Van der Hoek, K.H., Ritter, L.J., Armstrong, D.T., Magoffin, D.A.,

Dupont, J., Chabrolle, C., Ramé, C., Tosca, L., & Coyral-Castel, S. (2008). Role of the

Enyedi, P., Szabó, B. & Spät, A. (1983) Failure of vasoactive intestinal peptide to stimulate

Espenshade, P. J, & Hughes, A.L. (2007). Regulation of sterol synthesis in eukaryotes. *Annual* 

Flores, A., Gallegos, A. I., Velasco, J., Mendoza, F. D., Montiel, C., Everardo, P. M., Cruz, M.

Flores, A., Meléndez, G., Palafox, M. T., Rodríguez, J., Barco, A. I., Chavira, R., Domínguez,

Flores, A., Velasco, J., Gallego,s A. I., Mendoza, F. D., Everardo, P. M., Cruz, M. E. &

Frungieri, M. B., Zitta, K., Pignataro, O. P., Gonzalez-Calvar, S. I. & Calandra, R. S. (2002).

*and Endocrinology,* Vol. 9, No.34, (March 2011), pp. , ISSN 1945-7170. Franchimont, P. (1983). Regulation of gonadal androgen secretion. *Hormone Research,* Vol.18,

*Review of Genetics,* Vol.41, (July 2007), pp. 401-427, ISSN: 0066-4197.

Press, New York

ISSN 1470-1626.

79.ISSN 0231-424X

11, ISSN 1945-7170.

No. 1-3, pp.7-17, ISSN 1423-0046.

35-46, ISSN 0028-3835.

1687-4765.

*Biological Sciences*. Vol.5, No. Pp. 95-104

*Factors and the Ovary.* Editor Anne M.Hirshfield.. Chap. 39. pp.321-325. Plenum

& Norman R.J. (2002) Effects of leptin administration and feed restriction on thecal leucocytes in the preovulatory rat ovary and the effects of leptin on meiotic maturation, granulosa cell proliferation, steroid hormone and PGE2 release in cultured rat ovarian follicles. *Reproduction,* Vol. 123, No.6, (June 2002), pp. 891-898,

peroxisome proliferator-activated receptors, adenosine monophosphate-activated kinase, and adiponectin in the ovary. *PPAR Research,* Vol. 2008, p. 176275 , ISSN

aldosterone production. *Acta Physiologica Hungarica*. Vol. 61, No. 1-2, (n.d.)pp. 77-

E., Domínguez, R. (2008). The acute effects of bilateral ovariectomy or adrenalectomy on progesterone, testosterone and estradiol serum levels depend on the surgical approach and the day of the estrous cycle when they are performed. *Reproductive Biology and Endocrinology,* Vol. 6. (October 2011), p. 48, ISSN 1945-7170.

R. & Cruz, M. E. (2005). The participation of the cholinergic system in regulating progesterone secretion through the ovarian-adrenal crosstalk varies along the estrous cycle*. Endocrine,* Vol. 28, No.2, (July 2005), pp. : 145-151, ISSN 1559-0100. Flores, A., Rodríguez, J. O., Palafox, M. T., Meléndez, G., Barco, A. I., Chavira, R., Cruz, M.

E. & Domínguez, R. (2006). The acute asymmetric effects of hemiovariectomy on testosterone secretion vary along the estrous cycle. The participation of the cholinergic system. *Reproductive Biology and Endocrinology,* Vol. 4, (March 2006), p.

Domínguez, R. (2011). Acute effects of unilateral sectioning the superior ovarian nerve of rats with unilateral ovariectomy on ovarian hormones (progesterone, testosterone and estradiol) levels vary during the estrous cycle. *Reproductive Biology* 

Interactions between testicular serotoninergic, catecholaminergic, and corticotropin-releasing hormone e systems modulating cAMP and testosterone production in the golden hamster. *Neuroendocrinology.* Vol.17, No.1, (July 2002), pp.


Hormonal and Neural Mechanisms Regulating Hormone Steroids Secretion 31

Malendowicz, L. K., Neri, G., Markowska, A., Hochol, A., Nussdorfer, G. G. & Majchrzak,

*Biology,* Vol. 87, No. 4-5, (December 2003), pp. 265-2688, ISSN 0960-0760. Manna, P.R., Kero J., Tena-Sempere, M., Pakarinen, P., Stocco, D.M., & Huhtaniemi, I.T.

Manna, P.R., Tena-Sempere, M., Huhtaniemi, I.T. (1999). Molecular mechanisms of thyroid

Maran, R.R., Arunakaran, J. & Aruldhas, M.M. (2000). T3 directly stimulates basal and

Markowska, A., Neri, G., Hochol,A., Nowak, M., Nussdorfer ,G.G., & Malendowicz, L.K.

Mavridou, S., Venihaki, M., Rassouli, O., Tsatsani,s C., & Kardassis D. (2010). Feedback

Mayerhofer, A., Dissen, G. A., Costa, M. E., & Ojeda, S. R. (1997). A role for

*Endocrinology,* Vol.138, No.9, (August 1997), pp. 3320-3329, ISSN 1945-7170. Mazzocchi, G., Rebuffat, P., Meneghelli, V., Malendowicz, L.K., Tortorella, C., Gottard,o G.,

Mészárosová, M., Sirotkin, A.V., Grossmann, R., Darlak, K., & Valenzuela, F. (2008). The

Miszkiel, G., & Kotwica, J. (2001). Mechanism of action of noradrenaline on secretion of

Morales-Ledesma, L., Ramírez, D.A., Vieyra, E., Trujillo, A., Chavira, R., Cárdenas, M. &

*Biology and Endocrinology.* Vol. 9, (March 30 2011), p. 41, ISSN 1477-7827. Morán, C., Franco, A., Morán, J,L,, Handal, A,, Morales, L, & Domínguez R. (2005). Neural

Vol. 108, No. 1-2, (October 2008), pp. 196-207, ISSN 0378-4320.

*Hungarica*, Vol.49, No.1, pp. 39-51, ISSN 1588-2705.

Vol. 13, No.1, (January 2004), pp. 139-141, ISSN 1107-3756.

2001), pp. 319-31, ISSN 1945-7170.

2010), pp. 3214-24, ISSN 1945-7170.

594 , ISSN 0196-9781.

ISNN0013-7219.

(February 26), pp. 5909–5918, ISSN 1083-351X.

M. (2003). Effects of leptin and leptin fragments on steroid secretion of freshly dispersed rat adrenocortical cells. *The Journal of Steroid Biochemistry & Molecular* 

(2001). Assessment of mechanisms of thyroid hormone action in mouse Leydig cells: regulation of the steroidogenic acute regulatory protein, steroidogenesis, and luteinizing hormone receptor function. *Endocrinology,* Vol. 142, No.1, (January

hormone-stimulated steroidogenesis: involvement of steroidogenic acute regulatory (StAR) protein. Journal of Biological Chemistry. Vol. 274, No.,9

modulates LH induced testosterone and oestradiol production by rat Leydig cells in vitro. *Endocrinologia Japonica*. Vol. 47, No. 4 (August 2000), pp.417-428,

(2004). Effects of leptin and leptin fragments on steroid secretion and proliferative activity of regenerating rat adrenal cortex. *International Journal of Molecular Medicine*

inhibition of human scavenger receptor class B type I gene expression by glucocorticoid in adrenal and ovarian cells. *Endocrinology,* Vol. 151, No.7, (July

neurotransmitters in early follicular development: induction of functional folliclestimulating hormone receptors in newly formed follicles of the rat ovary.

& Nussdorfer, G. G. (1999). Gastric inhibitory polypeptide stimulates glucocorticoid secretion in rats, acting through specific receptors coupled with the adenylate cyclase-dependent signaling pathway. *Peptides,* Vol.20 , ( 1999), pp. 589-

effect of obestatin on porcine ovarian granulosa cells. *Animal Reproduction Science*,

progesterone and oxytocin by the bovine corpus luteum in vitro. *Acta Veterinaria* 

Domínguez R. (2011). Effects of acute unilateral ovariectomy to pre-pubertal rats on steroid hormones secretion and compensatory ovarian responses. *Reproductive* 

activity between ovaries and the prevertebral celiac-superior mesenteric ganglia

steroidogenesis in cultured human lutein granulosa cells. *Journal of Endocrinological Investigation*, Vol.32, No.5, (May 2009), pp. 415-419, ISSN 0022-0795.


*Investigation*, Vol.32, No.5, (May 2009), pp. 415-419, ISSN 0022-0795. Kawakami, M., Kubo K., Uemura, T. & Nagase, M.(1979). Evidence for the existence of

pp. 136-145, ISSN 1945-7170.

pp. 453–481, ISSN 0004-0681.

pp.818-826, ISSN 0013-7227.

ISSN 1432-0878.

ISNN0013-7219

7268.

(February 1988), pp. 217-222 , ISSN 0304-3940.

No.2, (April 2011), pp. 397-407, ISSN 10966080.

steroidogenesis in cultured human lutein granulosa cells. *Journal of Endocrinological*

extra-hypophyseal neural mechanisms controlling ovarian steroid secretion. *Journal of Steroid Biochemistry*, Vol.11, No.1C, (July 1979), pp. 1001-1005, ISSN 0022-4731. Kawakami, M., Kubo, K., Uemura, T., Nagase, M. &, Hayashy, R.(1981). Involvement of

ovarian innervation on steroid secretion. *Endocrinology*, Vol. 109, No.1, (July 1981),

sympathetic neurons innervating the rat ovary. *Neuroscience Letters,* Vol.85 , No.2,

adrenal gland. *Archivum Histologicum Japonicum,* Vol. 48, No.5, (December 1985),

Pharmacological doses of testosterone up-regulated androgen receptor (AR) and 3 beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase (3{beta}HSD) and impaired Leydig cells steroidogenesis in adult rat. *Toxicological Sciences,* Vol.120,

immunoreactivity in scattered chromaffin cells and nerve fibers in the adrenal gland of rats. *Cell & Tissue Research*, Vol. 247, No.2, (February 1987), pp. 309-315,

(1999). Gonadotropin stimulation of pituitary adenylate cyclase-activating polypeptide (PACAP) messenger ribonucleic acid in the rat ovary and the role of PACAP as a follicle survival factor. *Endocrinology.* Vol. 140, No. 2 (February 1999),

induced ovulation and steroidogenesis by short-term hyperprolactinemia in female rabbits. *Endocrinologia Japonica,* Vol. 34, No. 5, (October 1997), pp. 675-683,

hormone in regulating gene expression during selection of a dominant follicle in cattle. *Biology of Reproduction,* Vol.84, No.2, (February 2011), pp. 369-78, ISSN 1529-

regulators on secretory activity of porcine granulosa cells in vitro. *Animal Reproduction Science*, Vol.81 , No.1-2, (March 2004), pp. 125-36, ISSN 0378-4320. Malendowicz, L. K. Rucinsk, M., Belloni, A.S, Ziolkowska, A. & Nussdorfer, G. G. (2007).

Leptin and the regulation of the hypothalamic-pituitary-adrenal axis. *International* 

corticosterone secretion of rat adrenocortical cells, through the activation of the adenylate cyclase-dependent signaling cascade. *The Journal of Steroid Biochemistry & Molecular Biology,* Vol. 70, No.4-6, (Sep-October 1999), pp. 185-188, ISSN 0960-0760.

Klein, C. M. & Burden, H. W. (1988). Anatomical localization of afferent and postganglionic

Kondo, H. (1985). Immunohistochemical analysis of the localizationof neuropeptides in the

Kostic, T. S., Stojkov, N. J., Bjelic, M. M., Mihajlovic, A. I., Janjic, M. M. & Andric, S. A. (2011)

Kuramoto, H., Kondo, H., & Fujita, T. (1987). Calcitonin gene-related peptide (CGRP)-like

Lee, J., Park, H.J., Choi, H.S., Kwon, H.B., Arimura, A., Lee, B,J,, Choi, W.S. & Chun S.Y.

Lin, K.C., Okamura, H. & Mori T. (1997). Inhibition of human chorionic gonadotropin-

Luo, W., Gumen, A., Haughian, J. M. & Wiltbank, M. . (2011). The role of luteinizing

Makarevich, A.V., Sirotkin, A.V., & Genieser, H.G. (2004). Action of protein kinase A

*Reviews of Cytology,* Vol. 263, (August 2007), pp. 63-102, ISSN 0074-7696. Malendowicz, L.K., Tortorella, C., & Nussdorfer, G. G. (1999). Orexins stimulate


Hormonal and Neural Mechanisms Regulating Hormone Steroids Secretion 33

Spiga, F, Liu, Y., Aguilera, G. & Lightman, S.L. (2011). Temporal effect of

Spinazzi, R., Andreis, P.G., Rossi, G.P. & Nussdorfe,r G.G. (2006). Orexins in the regulation

Stocco, C. (2008). Aromatase expression in the ovary: hormonal and molecular regulation.

Strauss, J. R- III & Hsueh, A. J. W. (2000). *Ovarian hormone synthesis*. In: *Endocrinology* Fourth

Sugawara, T., Kiriakidou, M., McAllister, J. M., Holt, J. A., Arakane, F. & Strauss, J. F. 3rd.

Szalay, K. S, Orsó, E., Jurányi, Z., Vinson, G. . & Vizi, E. S. (1998). Local non-synaptic

Tortorella, C., Neri, G. & Nussdorfer, G.G. (2007). Galanin in the regulation of the

Tóth I.E., Wiesel O., Boldogkoi, Z., Bálint, K., Tapaszti, Z. & Gerendai, I. (2007).

Tropea, A., Lanzone, A., Tiberi,F., Romani, F., Catino, S. & Apa, R. (2010). Estrogens and

Trujillo, A., Morales, L., Dominguez, R. & Vindrola, O. (2001). Effects of sensorial

Trujillo, A., Morales, L., Vargas, X., Alba, L. & Domínguez R. (2004). Effects of capsaicin

Uchida, S., Kagitani F., Hotta, H., Hanada, T. & Aikawa, Y. (2005). Cutaneous mechanical

*Medicine*, Vol.19 , No.4, (April 2007), pp. 639-647, ISSN 1107-3756.

*Technique*. Vol. 70, No.8, (August 2007), pp.710-718, ISSN 1097-0029. Tóth, I.E., Wiesel, O., Boldogkoi, Z., Bálint, K., Tapaszti, Z. & Gerendai I. (2007).

*Technique*. Vol. 70, No. 8 (August 2007), pp.710-718 ISSN 1097-0029.

*Steroid,* Vol.73 , No.5, (May 2008), pp.473-478 , ISSN 0039-128x.

Saunders Co. ISBN 0-7216-7840-8 (set). Philadelphia, Pennsylvania

136-142, ISSN 0028-3835.

1997), pp.5-9, ISSN 0039-128x.

ISSN: 1559-0100.

No.6-7, (June-July), pp. 323-328, ISSN 0018-5043.

(November 2010), pp. 2257-2263, ISSN 0015-0282.

Neuroscience Meeting Planner. San Diego, Ca; 2001.

(October 2005), pp.265-277, ISSN 1881-1396.

March 2006), pp.46-57, ISSN 1521-0081.

adrenocorticotrophic hormone on adrenal glucocorticoid steroidogenesis: involvement of the transducer of regulated cyclic AMP-response element-binding protein activity. *Journal of Neuroendocrinology,* Vol. 23, No.2, (February 2001), pp.

of the hypothalamic-pituitary-adrenal axis. *Pharmacological Reviews*, Vol.58 , No.1, (

Edition edited by LJ De Groot and JL Jameson vol 3, Chap. 148, pp 2043-2052. WB

(1997). Regulation of expression of the steroidogenic acute regulatory protein (StAR) gene: a central role for steroidogenic factor 1. *Steroids,* Vol.62, No.1, (January

modulation of aldosterone production by catecholamines and ATP in rat: implications for a direct neuronal fine tuning. *Hormone Metabolic Research,* Vol.30,

hypothalamic-pituitary-adrenal axis (Review). *International Journal of Molecular* 

Predominance of supraspinal innervation of the left ovary. *Microscopic Research* 

Predominance of supraspinal innervation of the left ovary. *Microscopy Research* 

androgens affect human luteal cell function. *Fertility & Sterility,* Vol. 94, No. 6,

denervation on the ovarian functions in the adult rat. Program No. 734.14

treatment on the regulation of ovarian compensatory hypertrophy and compensatory ovulation. *Endocrine,* Vol. 25, No. 2, (November 2004), pp. 155-162,

stimulation regulates ovarian blood flow via activation of spinal and supraspinal reflex pathways in anesthetized rats. T*he Japanese journal of Physiology,* Vol. 55, No.5,

varies during the estrous cycle of the rat. *Endocrine* Vol. 26, No. 2 (March 2005), pp. 147-156, ISSN: 1559-0100.


Nimz, M., Spitschak, M., Fürbass, R., & Vanselow, J. (2010). The pre-ovulatory luteinizing

Niswender, G.D. (2002). Molecular control of luteal secretion of progesterone. *Reproduction*.

Nussdorfer, G.G., Bahçelioglu ,M., Neri, G. & Malendowicz, L.K. (2000). Secretin, glucagon,

Ramírez, D. A., Vieyra, E., Morales, L. & Dominguez, R. (2008). The acute effects of

Renshaw, D., Thomson, L.M., Carroll, M., Kapas. S. & Hinson J.P. (2000). Actions of

Rey-Ares, V., Lazarov, N., Berg, D., Berg, U., Kunz, L. & Mayerhofer, A. (2007). Dopamine

Ricci, A. G., Di Yorio, M. P. & Faletti, A. G. (2006). Inhibitory effect of leptin on the rat ovary

Ronti, T., Lupattelli. G. & Mannarino, E. (2006). The endocrine function of adipose tissue: an

Sirotkin, A.V., Makarevich, A.V. & Grosmann R. (2011). Protein kinases and ovarian

Sirotkin, A.V. & Grossmann, R. (2007a). The role of ghrelin and some intracellular

Sirotkin, A.V., & Grossmann, R. (2007b). Leptin directly controls proliferation, apoptosis and

Sirotkin, A.V, Makarevich A.V, & Grosmann ,R. (2011). Protein kinases and ovarian

Spicer, L. J . & Francisco, C. C. (1997). The adipose obese gene product, leptin: evidence of a

*Physiology*, Vol.147, No.1, (May 2007), pp. 239-246, ISSN 1531-4332.

Endocrinology. Vol.5 , (October 25), pp. 40, ISSN 1477-7827.

Vol. 123, No. 3 (March 2002), pp. 333-339, ISSN 1741-7899.

(February 2000), pp. 309-324, ISSN 0196-9781.

147-156, ISSN: 1559-0100.

pp. 1040-1048, ISSN 1098-2795.

Neuroscience; 2008, Online.

771-780, ISSN 1741-7899

0300-0664.

INSS 1097-4652.

2000), pp. 169-173, ISSN 1945-7170.

2007), pp.422-429, ISSN 1531-4332.

2011), pp. 37-45, ISSN 0095-9898.

1997), pp. 3374-3379, ISSN 1945-7170.

varies during the estrous cycle of the rat. *Endocrine* Vol. 26, No. 2 (March 2005), pp.

hormone surge is followed by down-regulation of CYP19A1, HSD3B1, and CYP17A1 and chromatin condensation of the corresponding promoters in bovine follicles. *Molecular Reproduction and Development,* Vol.77, No.12, (December 2010),

gastric inhibitory polypeptide, parathyroid hormone, and related peptides in the regulation of the hypothalamus- pituitary-adrenal axis. *Peptides,* Vol. 21, No.12,

unilateral ovariectomy to prepubertal rats on gonadotropin and hormone ovarian secretion are asymmetric. Program No. 81.3 Washington, DC: Society for

neuropeptide Y on the rat adrenal cortex. *Endocrinology*. Vol. 141, No. 1 (January

receptor repertoire of human granulosa cells. Reproductive Biology &

during the ovulatory process. *Reproduction,* Vol. 132, No. 5, (November 2006), pp.

update. *Clinical Endocrinology (Oxf).* 2006 Vol. 64, No.4, (April), pp.355-365. ISSN

functions. Journal of Cellular Physiology. Vol. 226, No. 1(September), pp. 37-45,

mechanisms in controlling the secretory activity of chicken ovarian cells. Comparative Biochemistry and Physiology. Part A. *Molecular & Integrative* 

secretory activity of cultured chicken ovarian cells. Comparative Biochemistry and Physiology. Part A. *Molecular & Integrative Physiology*. Vol. 148, No.2, (October

functions. *Journal of Cellular and Comparative Physiology,* Vol.226, No.1, (January

direct inhibitory role in ovarian function. *Endocrinology,* Vol. 138, No.8, (August


**2** 

**The Tissue Specific Role** 

Karin Tamm1,2,3, Marina Suhorutshenko1, Miia Rõõm1, Jaak Simm1 and Madis Metsis1,2

*3Nova Vita Clinic, Tallinn,* 

*Estonia* 

**of Estrogen and Progesterone** 

**in Human Endometrium and Mammary Gland** 

*1Centre for Biology of Integrated Systems, Tallinn University of Technology, Tallinn,* 

The purpose of this chapter is to review the tissue-specific role of estrogen (E2) and progesterone (P4) in human endometrium and mammary gland. It is well known that both E2 and P4 are essential for the development and differentiation of human endometrium and mammary gland, but the exact basis for differential tissue-specific signalling of E2 and P4 are still not fully understood. This chapter explores observed functions of two major female steroid hormones and their cognate receptors in normal physiology of human reproductive

The normal reproductive physiology requires tightly coordinated action of hypothalamus, pituitary gland, ovaries and endometrium. Also functioning of other endocrine units such as the thyroid and adrenal glands are essential for regular ovulation and cyclic changes. The production of ovarian steroid hormones is coordinated by the hypothalamic-pituitarygonadal axis which is activated in puberty (Figure 1). The hypothalamus produces and secretes luteinizing hormone-releasing hormone (LHRH), which binds to its receptors in pituitary gland. This causes cascade of biochemical events culminating in the production of two hormones in pituitary gland, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH and FSH are secreted into the general blood circulation and attach to receptors on the ovary, where they trigger ovulation and stimulate the production of E2 and P4. Ovarian steroid hormones themselves have direct role in the development of the inner lining of the uterus but they also act as a positive feedback system to hypothalamus and pituitary gland for continuous cyclic changes until the beginning of menopause (Kanis and

Cholesterol is the building block for all steroid hormones, which is carried into the bloodstream and through a sequence of enzymatic changes is synthesized into final products. In the bloodstream steroid hormones are distributed rapidly throughout the tissues and act on distant targets. This secretory process is called endocrine action and the function of many target tissues as mammary gland, brain, bones, liver and heart are affected by circulating hormones. Steroid hormones can also act very close to their site of secretion

system but also in assisted reproductive technology and breast cancer treatment.

**1. Introduction** 

Stevenson, 1994).

*2Competence Centre on Reproductive Medicine and Biology, Tartu,* 

