Expression of estrogen receptor-alpha and cFos in norepinephrine and epinephrine neurons of young and middle-aged rats during the steroid-induced luteinizing hormone surge.

Norepinephrine (NE) and epinephrine are important stimulators of GnRH release during the preovulatory surge in female rats. Previous studies have shown that the catecholaminergic neurons are sensitive to estradiol and that NE release in the hypothalamus is decreased in middle-aged rats at the time when the estrous cycles become irregular and later cease to exist. The aims of the present study were to determine whether the NE and epinephrine neurons continue to express estrogen receptor (ER)-alpha in middle-aged rats; temporal expression of ER-alpha and cFos changes with age during the steroid-induced surge; and tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanol-N-methyltransferase mRNA content in catecholaminergic neurons of the brain stem changes during the surge with age. The results show that there was no difference in TH mRNA content; however, DBH mRNA levels in areas A1, A2, and C1 of the middle-aged animals did not rise during the surge as was observed in the young animals. Although the percentage of NE and epinephrine neurons that express ER-alpha was unchanged during the surge in both young and middle-aged animals, cFos expression was enhanced in areas A1 and A2 of the middle-aged animals but not in the young animals. Together the results suggest that NE and epinephrine neurons in the middle-aged rat continue to express appropriate basal levels of TH, DBH, and phenylethanol-N-methyltransferase mRNAs as well as ER-alpha and cFos; however, the enhancement of DBH expression, as seen in the young animals during the steroid-induced surge, was not detected in middle-aged animals. On the other hand, cFos expression in the middle-aged rat was higher in areas A1 and A2 during the surge. It is concluded that the reduced catecholamine release during the surge in middle-aged rats is caused, in part, by an altered sensitivity of the NE neurons to estradiol, which results in an aberrant cFos expression and probably not by major deficits in the expression of transmitter synthesizing enzymes or steroid receptors.

[1]  A. Herbison,et al.  Differential expression of estrogen receptor and neuropeptide Y by brainstem A1 and A2 noradrenaline neurons , 1997, Neuroscience.

[2]  D. Pfaff,et al.  Alpha 1 adrenergic regulation of estrogen-induced increases in luteinizing hormone-releasing hormone mRNA levels and release. , 1993, Brain research. Molecular brain research.

[3]  S. Kalra,et al.  Effects of intraventricular administration of catecholamines on luteinizing hormone release in morphine-treated rats. , 1983, Endocrinology.

[4]  S. Kalra,et al.  Effects of drugs modifying catecholamine synthesis on plasma LH and ovulation in the rat. , 1974, Neuroendocrinology.

[5]  S R M REYNOLDS,et al.  Physiology of reproduction. , 1948, Annual review of physiology.

[6]  C. Coen,et al.  Effects of manipulating catecholamines on the incidence of the preovulatory surge of luteinizing hormone and ovulation in the rat: Evidence for a necessary involvement of hypothalamic adrenaline in the normal or ‘midnight’ surge , 1983, Neuroscience.

[7]  M. Baumert,et al.  Preoptic catecholamine, GABA, and glutamate release in ovariectomized and ovariectomized estrogen-primed rats utilizing a push-pull cannula technique. , 1985, Neuroendocrinology.

[8]  J. Rawson,et al.  Noradrenergic Projections from the A1 Field to the Preoptic Area in the Brain of the Ewe and Fos Responses to Oestrogen in the A1 Cells , 2001, Journal of neuroendocrinology.

[9]  C. Barraclough,et al.  Effects of estradiol and progesterone on catecholamine turnover rates in discrete hypothalamic regions in ovariectomized rats. , 1981, Endocrinology.

[10]  P. MohanKumar,et al.  Correlations of catecholamine release in the medial preoptic area with proestrous surges of luteinizing hormone and prolactin: effects of aging. , 1994, Endocrinology.

[11]  M. Miller,et al.  Ovariectomy and age alter gonadotropin hormone releasing hormone noradrenergic interactions , 1995, Neurobiology of Aging.

[12]  K. Kitahama,et al.  Immunohistochemical evidence for the adrenergic medullary longitudinal bundle as a major ascending pathway to the locus coeruleus , 1987, Neuroscience Letters.

[13]  S. Kalra,et al.  Involvement of norepinephrine in transmission of the stimulatory influence of progesterone on gonadotropin release. , 1972, Endocrinology.

[14]  W. R. Crowley,et al.  Effects of an epinephrine synthesis inhibitor, SKF64139, on the secretion of luteinizing hormone in ovariectomized female rats , 1981, Brain Research.

[15]  L. Grant,et al.  3H estradiol in catecholamine neurons of rat brain stem: Combined localization by autoradiography and formaldehyde‐induced fluorescence , 1977, The Journal of comparative neurology.

[16]  J. D. Neill,et al.  The Physiology of reproduction , 1988 .

[17]  Á. Simonyi,et al.  Effect of phenylethanolamine N-methyltransferase inhibition on serum concentrations of luteinizing hormone, follicle stimulating hormone and prolactin in pro-oestrous and ovariectomized rats , 1985, Brain Research.

[18]  D. Clifton,et al.  LH release and ovulation in the rat following depletion of hypothalamic norepinephrine: chronic vs. acute effects. , 1979, Neuroendocrinology.

[19]  C. D. Stern,et al.  Handbook of Chemical Neuroanatomy Methods in Chemical Neuroanatomy. Edited by A. Bjorklund and T. Hokfelt. Elsevier, Amsterdam, 1983. Cloth bound, 548 pp. UK £140. (Volume 1 in the series). , 1986, Neurochemistry International.

[20]  P. Wise,et al.  Neuroendocrine influences on aging of the female reproductive system , 1991 .

[21]  P. MohanKumar,et al.  Cyclic and age-related changes in norepinephrine concentrations in the medial preoptic area and arcuate nucleus , 1995, Brain Research Bulletin.

[22]  M. Johnson,et al.  Evidence for the involvement of central epinephrine systems in the regulation of luteinizing hormone, prolactin, and growth hormone release in female rats. , 1982, Endocrinology.

[23]  K. Kitahama,et al.  Immunohistochemical evidence for the adrenergic medullary longitudinal bundle as a major ascending pathway to the hypothalamus , 1987, Neuroscience Letters.

[24]  L. Jennes,et al.  Expression of estrogen receptor-α and c-Fos in adrenergic neurons of the female rat during the steroid-induced LH surge , 2000, Brain Research.

[25]  P. Wise,et al.  Norepinephrine and dopamine activity in microdissected brain areas of the middle-aged and young rat on proestrus. , 1982, Biology of reproduction.

[26]  S. Mccann,et al.  Re-evaluation of the role of catecholamines in control of gonadotropin and prolactin release. , 1978, Neuroendocrinology.

[27]  Mahlon D. Johnson,et al.  Evidence that norepinephrine and epinephrine systems mediate the stimulatory effects of ovarian hormones on luteinizing hormone and luteinizing hormone-releasing hormone. , 1983, Endocrinology.

[28]  D. Pfaff,et al.  Tyrosine hydroxylase mRNA in the neurons of the tuberoinfundibular region and zona incerta examined after gonadal steroid hormone treatment. , 1989, Molecular endocrinology.

[29]  A. Herbison,et al.  Identification and characterization of estrogen receptor α‐containing neurons projecting to the vicinity of the gonadotropin‐releasing hormone perikarya in the rostral preoptic area of the rat , 1999, The Journal of comparative neurology.

[30]  M. Miller,et al.  Estrogen regulates galanin but not tyrosine hydroxylase gene expression in the rat locus ceruleus. , 1997, Brain research. Molecular brain research.

[31]  E. Laplante,et al.  alpha 1-adrenergic receptor involvement in the LH surge in ovariectomized estrogen-primed rats. , 1982, European journal of pharmacology.

[32]  R. Gallo,et al.  Effect of intraventricular infusion of catecholamines on luteinizing hormone release in ovariectomized and ovariectomized, steroid-primed rats. , 1979, Neuroendocrinology.

[33]  C. Sawyer,et al.  Role of catecholamines in stimulating the release of pituitary ovulating hormone(s) in rats. , 1970, Endocrinology.

[34]  K. Pau,et al.  Oestrogen Upregulates Noradrenaline Release in the Mediobasal Hypothalamus and Tyrosine Hydroxylase Gene Expression in the Brainstem of Ovariectomized Rhesus Macaques , 2000, Journal of neuroendocrinology.

[35]  Z. Liposits,et al.  Detection of Estrogen Receptor-β Messenger Ribonucleic Acid and 125I-Estrogen Binding Sites in Luteinizing Hormone-Releasing Hormone Neurons of the Rat Brain. , 2000, Endocrinology.

[36]  W. Le,et al.  Alpha1-adrenergic receptor blockade blocks LH secretion but not LHRH cFos activation , 1997, Brain Research.

[37]  R. Goodman.  A quantitative analysis of the physiological role of estradiol and progesterone in the control of tonic and surge secretion of luteinizing hormone in the rat. , 1978, Endocrinology.

[38]  H. Kaba,et al.  Effects of estrogen on the excitability of neurons projecting from the noradrenergic A1 region to the preoptic and anterior hypothalamic area , 1983, Brain Research.

[39]  A. Herbison,et al.  Oestrogen modulation of noradrenaline neurotransmission. , 2000, Novartis Foundation symposium.

[40]  P. Shughrue,et al.  Comparative distribution of estrogen receptor‐α and ‐β mRNA in the rat central nervous system , 1997, The Journal of comparative neurology.

[41]  C. Barraclough,et al.  Tyrosine Hydroxylase Messenger Ribonucleic Acid Levels Increase in A1 but not Locus Ceruleus Noradrenergic Neurons in Proestrous Rats but not in Diestrous or Androgen‐Sterilized Animals , 1992, Journal of neuroendocrinology.

[42]  A. Herbison,et al.  Fluctuating estrogen and progesterone receptor expression in brainstem norepinephrine neurons through the rat estrous cycle. , 1999, Endocrinology.

[43]  C. Barraclough,et al.  Temporal changes in tyrosine hydroxylase mRNA levels in A1, A2 and locus ceruleus neurons following electrical stimulation of A1 noradrenergic neurons. , 1992, Brain research. Molecular brain research.

[44]  C. Purvis,et al.  c-fos expression in noradrenergic A2 neurons of the rat during the estrous cycle and after steroid hormone treatments , 1992, Brain Research.

[45]  B. K. Hartman,et al.  The central adrenergic system. An immunofluorescence study of the location of cell bodies and their efferent connections in the rat utilizing dopamine‐B‐hydroxylase as a marker , 1975, The Journal of comparative neurology.

[46]  L. Jennes,et al.  Identification of α1b Adrenergic Receptor Protein in Gonadotropin Releasing Hormone Neurones of the Female Rat , 1998, Journal of neuroendocrinology.