Endocrinology, Vol 114, 930-940, Copyright © 1984 by Endocrine Society

ARTICLES

A quantitative analysis of the roles of dosage, sequence, and duration of estradiol and progesterone exposure in the regulation of maternal behavior in the rat

RS Bridges

The regulation of the onset of maternal behavior in the rat is under hormonal control. This study reports a new endocrine model for the study of the hormonal regulation of maternal responsiveness. The model employs the administration of physiological amounts of the steroids estradiol (E2) and progesterone (P) via Silastic implants to inexperienced nulliparous rats and measurement of the effects of these implants on maternal behavior. In the first two experiments, the levels of E2 and P in the sera of pregnant and hormone-treated rats were measured by RIA. Using known physiological treatments of E2 given in combination with P, the effects of E2 and P on maternal behavior were measured. Treatment with a combination of E2 at all dosages plus P for 2 weeks before P removal and behavioral testing stimulated a fast onset of maternal behavior in ovariectomized nulliparous rats. Exposure for 2 weeks to small E2 implants (1 or 2 mm; approximately 20-30 pg/ml serum) did not affect maternal responsiveness, whereas large E2 implants (10 mm; approximately 110 pg/ml serum) stimulated maternal behavior. P treatment alone had no behavioral effect. Simultaneous removal of E2 plus P before exposure to foster young also resulted in a stimulation of behavioral responsiveness, indicating that the presence of elevated titers of circulating E2 is not a requirement for stimulation to occur. In addition to facilitating a rapid onset of behavior, the quality of the response in steroid-primed rats was similar to that measured in lactating rats in a T-maze test. In another experiment, when female rats were treated with P before E2 administration, maternal behavior was rapidly induced. Thus, P itself can sensitize the female to the behavioral effects of E2. Finally, the duration of steroid-exposure before testing was found to influence maternal behavior. Increased durations of E2 plus P exposure before testing were accompanied by decreased latencies to respond maternally to foster young. These data indicate that during pregnancy, E2 and P prime the female to respond to her young at birth. The intensity of the steroidal priming increases as pregnancy progresses, and this primed potential is subsequently unmasked by the decline in P and the maintenance of E2 secretion around parturition. These findings demonstrate that behavioral processes can be modified in the adult animal as a result of long term changes in endocrine state, i.e. pregnancy.

This article has been cited by other articles:

				D. T. Theodosis, D. A. Poulain, and S. H. R. Oliet Activity-Dependent Structural and Functional Plasticity of Astrocyte-Neuron Interactions Physiol Rev, July 1, 2008; 88(3): 983 - 1008. [Abstract] [Full Text] [PDF]

				F. J. Steyn, G. M. Anderson, and D. R. Grattan Hormonal Regulation of Suppressors of Cytokine Signaling (SOCS) Messenger Ribonucleic Acid in the Arcuate Nucleus during Late Pregnancy Endocrinology, June 1, 2008; 149(6): 3206 - 3214. [Abstract] [Full Text] [PDF]

				S. M. Yellon, C. A. Ebner, and Y. Sugimoto Parturition and Recruitment of Macrophages in Cervix of Mice Lacking the Prostaglandin F Receptor Biol Reprod, March 1, 2008; 78(3): 438 - 444. [Abstract] [Full Text] [PDF]

				D. S. Gupta, H. von Gizycki, and A. R. Gintzler Sex-/Ovarian Steroid-Dependent Release of Endomorphin 2 from Spinal Cord J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 635 - 641. [Abstract] [Full Text] [PDF]

				S. Pillet, M. D'Elia, J. Bernier, J.-M. Bouquegneau, M. Fournier, and D. G. Cyr Immunomodulatory Effects of Estradiol and Cadmium in Adult Female Rats Toxicol. Sci., August 1, 2006; 92(2): 423 - 432. [Abstract] [Full Text] [PDF]

				W. E. Armstrong and G. I. Hatton The puzzle of pulsatile oxytocin secretion during lactation: some new pieces Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2006; 291(1): R26 - R28. [Full Text] [PDF]

				S. L. Bealer, D. L. Lipschitz, G. Ramoz, and W. R. Crowley Oxytocin receptor binding in the hypothalamus during gestation in rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2006; 291(1): R53 - R58. [Abstract] [Full Text] [PDF]

				M. L. Ruiz, S. S. M. Villanueva, M. G. Luquita, M. Vore, A. D. Mottino, and V. A. Catania ETHYNYLESTRADIOL INCREASES EXPRESSION AND ACTIVITY OF RAT LIVER MRP3 Drug Metab. Dispos., June 1, 2006; 34(6): 1030 - 1034. [Abstract] [Full Text] [PDF]

				D. T. Theodosis, A. Trailin, and D. A. Poulain Remodeling of astrocytes, a prerequisite for synapse turnover in the adult brain? Insights from the oxytocin system of the hypothalamus Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1175 - R1182. [Abstract] [Full Text] [PDF]

				R. Teruyama and W. E Armstrong Enhancement of calcium-dependent afterpotentials in oxytocin neurons of the rat supraoptic nucleus during lactation J. Physiol., July 15, 2005; 566(2): 505 - 518. [Abstract] [Full Text] [PDF]

				L.-J. Xiao, J.-X. Yuan, Y.-C. Li, R. Wang, Z.-Y. Hu, and Y.-X. Liu Extracellular Ca2+-sensing receptor expression and hormonal regulation in rat uterus during the peri-implantation period Reproduction, June 1, 2005; 129(6): 779 - 788. [Abstract] [Full Text] [PDF]

				M. Febo, C. F. Ferris, and A. C. Segarra Estrogen Influences Cocaine-Induced Blood Oxygen Level-Dependent Signal Changes in Female Rats J. Neurosci., February 2, 2005; 25(5): 1132 - 1136. [Abstract] [Full Text] [PDF]

				Y. Wang, R. Thuillier, and M. Culty Prenatal Estrogen Exposure Differentially Affects Estrogen Receptor-Associated Proteins in Rat Testis Gonocytes Biol Reprod, November 1, 2004; 71(5): 1652 - 1664. [Abstract] [Full Text] [PDF]

				C.N. Mowa and R.E. Papka The Role of Sensory Neurons in Cervical Ripening: Effects of Estrogen and Neuropeptides J. Histochem. Cytochem., October 1, 2004; 52(10): 1249 - 1258. [Abstract] [Full Text] [PDF]

				D. L. Lipschitz, W. R. Crowley, and S. L. Bealer Differential sensitivity of intranuclear and systemic oxytocin release to central noradrenergic receptor stimulation during mid- and late gestation in rats Am J Physiol Endocrinol Metab, September 1, 2004; 287(3): E523 - E528. [Abstract] [Full Text] [PDF]

				C. Maric, K. Sandberg, and C. Hinojosa-Laborde Glomerulosclerosis and Tubulointerstitial Fibrosis are Attenuated with 17{beta}-Estradiol in the Aging Dahl Salt Sensitive Rat J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1546 - 1556. [Abstract] [Full Text] [PDF]

				J. Cao, M. Wood, Y. Liu, T. Hoffman, J. Hyde, O.-K. Park-Sarge, and M. Vore Estradiol Represses Prolactin-Induced Expression of Na+/Taurocholate Cotransporting Polypeptide in Liver Cells through Estrogen Receptor-{alpha} and Signal Transducers and Activators of Transcription 5a Endocrinology, April 1, 2004; 145(4): 1739 - 1749. [Abstract] [Full Text] [PDF]

				F. A. Champagne, I. C. G. Weaver, J. Diorio, S. Sharma, and M. J. Meaney Natural Variations in Maternal Care Are Associated with Estrogen Receptor {alpha} Expression and Estrogen Sensitivity in the Medial Preoptic Area Endocrinology, November 1, 2003; 144(11): 4720 - 4724. [Abstract] [Full Text] [PDF]

				B. Greco, L. S. Lubbers, and J. D. Blaustein Estrogen Receptor {beta} Messenger Ribonucleic Acid Expression in the Forebrain of Proestrous, Pregnant, and Lactating Female Rats Endocrinology, May 1, 2003; 144(5): 1869 - 1875. [Abstract] [Full Text] [PDF]

				D. S. Gupta and A. R. Gintzler Influence of Ovarian Sex Steroids on Spinal Methionine-Enkephalin Release: Comparison with Dynorphin Reveals Asymmetrical Regulation J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 738 - 744. [Abstract] [Full Text] [PDF]

				S.-H. Li, H.-L. Huang, and Y.-H. Chen Ovarian Steroid-Regulated Synthesis and Secretion of Complement C3 and Factor B in Mouse Endometrium During the Natural Estrous Cycle and Pregnancy Period Biol Reprod, February 1, 2002; 66(2): 322 - 332. [Abstract] [Full Text] [PDF]

				F. Champagne, J. Diorio, S. Sharma, and M. J. Meaney Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors PNAS, October 12, 2001; (2001) 221224598. [Abstract] [Full Text] [PDF]

				J. Cao, P. M. Gowri, T. C. Ganguly, M. Wood, J. F. Hyde, F. Talamantes, and M. Vore PRL, Placental Lactogen, and GH Induce Na+/Taurocholate-Cotransporting Polypeptide Gene Expression by Activating Signal Transducer and Activator of Transcription-5 in Liver Cells Endocrinology, October 1, 2001; 142(10): 4212 - 4222. [Abstract] [Full Text] [PDF]

				M. Jankowski, G. Rachelska, W. Donghao, S. M. McCann, and J. Gutkowska Estrogen receptors activate atrial natriuretic peptide in the rat heart PNAS, September 13, 2001; (2001) 201394198. [Abstract] [Full Text] [PDF]

				D. S. Gupta, A. B. Kelson, W. E. Polgar, L. Toll, M. Szucs, and A. R. Gintzler Ovarian Sex Steroid-Dependent Plasticity of Nociceptin/Orphanin FQ and Opioid Modulation of Spinal Dynorphin Release J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1213 - 1220. [Abstract] [Full Text] [PDF]

				J. P. H. Burbach, S. M. Luckman, D. Murphy, and H. Gainer Gene Regulation in the Magnocellular Hypothalamo-Neurohypophysial System Physiol Rev, July 1, 2001; 81(3): 1197 - 1267. [Abstract] [Full Text] [PDF]

				R. S. Bridges, B. A. Rigero, E. M. Byrnes, L. Yang, and A. M. Walker Central Infusions of the Recombinant Human Prolactin Receptor Antagonist, S179D-PRL, Delay the Onset of Maternal Behavior in Steroid-Primed, Nulliparous Female Rats Endocrinology, February 1, 2001; 142(2): 730 - 739. [Abstract] [Full Text] [PDF]

				M. E. Freeman, B. Kanyicska, A. Lerant, and G. Nagy Prolactin: Structure, Function, and Regulation of Secretion Physiol Rev, October 1, 2000; 80(4): 1523 - 1631. [Abstract] [Full Text] [PDF]

				S. L. Sell, J. M. Scalzitti, M. L. Thomas, and K. A. Cunningham Influence of Ovarian Hormones and Estrous Cycle on the Behavioral Response to Cocaine in Female Rats J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 879 - 886. [Abstract] [Full Text]

				B. J. Blyth, R. L. Hauger, R. H. Purdy, and J. A. Amico The neurosteroid allopregnanolone modulates oxytocin expression in the hypothalamic paraventricular nucleus Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2000; 278(3): R684 - R691. [Abstract] [Full Text] [PDF]

				P. G. Green, S. R. Dahlqvist, W. M. Isenberg, H. J. Strausbaugh, F. J.-P. Miao, and J. D. Levine Sex Steroid Regulation of the Inflammatory Response: Sympathoadrenal Dependence in the Female Rat J. Neurosci., May 15, 1999; 19(10): 4082 - 4089. [Abstract] [Full Text] [PDF]

				R. S. Bridges, M. C. Robertson, R. P. C. Shiu, J. D. Sturgis, B. M. Henriquez, and P. E. Mann Central Lactogenic Regulation of Maternal Behavior in Rats: Steroid Dependence, Hormone Specificity, and Behavioral Potencies of Rat Prolactin and Rat Placental Lactogen I Endocrinology, February 1, 1997; 138(2): 756 - 763. [Abstract] [Full Text] [PDF]

				E.B. Keverne Psychopharmacology of maternal behaviour J Psychopharmacol, January 1, 1996; 10(1): 16 - 22. [PDF]

				R. Bridges, R DiBiase, D. Loundes, and P. Doherty Prolactin stimulation of maternal behavior in female rats Science, February 15, 1985; 227(4688): 782 - 784. [Abstract] [PDF]

				M. Jankowski, G. Rachelska, W. Donghao, S. M. McCann, and J. Gutkowska Estrogen receptors activate atrial natriuretic peptide in the rat heart PNAS, September 25, 2001; 98(20): 11765 - 11770. [Abstract] [Full Text] [PDF]

				F. Champagne, J. Diorio, S. Sharma, and M. J. Meaney Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors PNAS, October 23, 2001; 98(22): 12736 - 12741. [Abstract] [Full Text] [PDF]