Estrogen Alters Oxytocin mRNA Levels in the Preoptic Area

Abstract

Estrogen has numerous effects on immunoreactive levels of oxytocin (OXT) centrally, particularly in the preoptic lateral subcommissural nucleus (LSN). In this study in situ hybridization of a 38-base oligodeoxyribonucleotide (38mer) complementary to OXT mRNA revealed that estrogen treatment altered the pattern of OXT production in the rostral LSN and the more caudal anterior commissural nucleus. Rats were injected with 20 pg estradiol benzoate or sesame oil vehicle im 4 and 5 days after ovariectomy. On the sixth day all animals were perfused with paraformaldehyde-glutaraldehyde and their brains sectioned to 10 pm thickness in a -10 "C cryostat. Coronal brain sections were taken from four parallel levels of the preoptic-anterior hypothalamic area. These sections were mounted and hybridized insifu to a [1'25]-labeled 38mer for 16 h at 37 "C. Washed and dried slides were processed for autoradiography and analyzed with a light microscope. The effect of estrogen on OXT production differed between the rostral and caudal sections in both the LSN and periventricular (PeV) areas. Estrogen significantly increased OXT mRNA levels in LSN cells while decreasing hybridization in the anterior commissural nucleus cells. Changes in frequency patterns in the PeV paralleled those in the LSN with a significant drop of hybridization in the caudal PeV. Neurons hybridizing 38mer probe were also found in several other areas including the ventral medial preoptic area, lateral hypothalamus, bed nucleus of the stria terminalis and the nucleus triangularis septi. OXT mRNA levels were affected by estrogen treatments and this effect differed between the preoptic area and anterior hypothalamus. The sensitivity of LSN oxytocinergic cells to estrogen has implications for estrogen-sensitive OXT-enhanced reproductive behaviorsThe ovarian steroid estrogen influences oxytocin (OXT) physiology in the CNS. Estrogen treatments increase OXT release from Ihe posterior pituitary (1) and increase firing of oxytocinergic neurons in the paraventricular nucleus (PVN) (2). Levels of immunoreactive OXT in the PVN vary with estrous state in ways {hat suggest estrogen's influence (3). OXT immunoreactive levels :tho increase in the PVN and supraoptic nucleus (SON) peripar-I um as estrogen levels increase, while OXT levels in more rostral synthesis sites are decreasing (4).The preoptic area (POA) sites of OXT synthesis are particularly sensitive to estrogen influence. Estrogen implants increased OXT immunoreactive content in the POA (5). Short-term treatment with silastic implants of estradiol increased the number of OXT i~nmunostained cells in the periventricular (PeV) and dorsolateral I' OA as well as in several other sites (6). The collection of oxytocinergic cells ventrolateral of the anterior commissure in the dorsolateral POA and overlapping the septohypothalamic nucleus and bed nucleus of the stria terminalis (BnST) has been called the lateral subcommissural nucleus (LSN) (6, 7). Oxytocinergic cells in the LSN showed increased immunostaining after s...

Estrogen receptor‐β in oxytocin and vasopressin neurons of the rat and human hypothalamus: Immunocytochemical and in situ hybridization studies

“…Although estrogen response elements are present in the promoter regions of the OT-neurophysin (Mohr and Schmitz, 1991) and the VP-neurophysin (Shapiro et al, 2000) genes, the issue of whether estrogen can directly regulate OT and VP gene transcription in the PVH and in the SO is highly controversial (Caldwell et al, 1989;Miller et al, 1989;Burbach et al, 1990;Chung et al, 1991;Amico et al, 1995;Crowley et al, 1995;Nomura et al, 2002;Shughrue et al, 2002). Elevated levels of the mRNAs for OT and, to a lesser extent, for VP were observed during pregnancy and lactation (Lightman and Young, 1987;Van Tol et al, 1988;Zingg and Lefebvre, 1988;Crowley and Amico, 1993), but ovariectomy and estrogen replacement in earlier reports did not appear to significantly alter OT (Miller et al, 1989;Burbach et al, 1990;Amico et al, 1995) or VP (Roy et al, 1999) mRNA levels.…”

“…These include neuronal OT and VP mRNA expression (Van Tol et al, 1988;Caldwell et al, 1989;Nomura et al, 2002;Shughrue et al, 2002) and peptide (Jirikowski et al, 1988;Levin and Sawchenko, 1993) levels, serum (Skowsky et al, 1979;Yamaguchi et al, 1979), and pituitary (Van Tol et al, 1988;Levin and Sawchenko, 1993) levels of OT and VP, axonal (Crowley et al, 1978;Skowsky et al, 1979;Yamaguchi et al, 1979;Amico et al, 1981), and dendritic (Wang et al, 1995) release of OT, as well as the regulation of electrical activity of OT neurons (Negoro et al, 1973;Akaishi and Sakuma, 1985). The reported absence or only low level of expression of the classical estrogen receptor (ER-␣) in the PVH and the SO (Simerly et al, 1990;Shughrue et al, 1997) of the rat, together with recent identification of the second isoform of estrogen receptor (ER-␤) (Kuiper et al, 1996) within subsets of OT and VP neurons Alves et al, 1998;Hrabovszky et al, 1998;Laflamme et al, 1998;Shughrue et al, 2002;Somponpun and Sladek, 2003;Stern and Zhang, 2003), indicate that direct estrogen effects on OT and VP neurons may be primarily exerted via the newly discovered ER-␤.…”

Neuroanatomical distribution of androgen and estrogen receptor-immunoreactive cells in the brain of the male roughskin newt

“…The cellular events mediating many such changes appear to involve modulating the expression of specific genes within the brain (McEwen, 1991;McEwen et al, 1991). For example, testosterone and estradiol are thought to regulate arginine vasopressin, oxytocin, and proopiomelanocortin messenger RNA (mRNA) levels in specific brain regions (Caldwell et al, 1989;Chowen-Breed et al, 1989;Brot et al, 1993;Crowley and Amico, 1993). These gonadal steroids also affect the secretion of gonadotropins (Summerville and Schwartz, 1981;Fink et al, 19911, regulate receptor synthesis and density in discrete brain areas (Parsons et al, 1980;de Kloet et al, 1986;McEwen et al, 19911, affect neuronal morphology (Kurz et al, 1986;Gould et al, 1990;Matsumoto, 1991), and alter neuronal electrophysiology (Pfaff, 1981;Nabekura et al, 1986).…”

Social status in pairs of male squirrel monkeys determines the behavioral response to central oxytocin administration

“…At a behavioral level, OT's effects on maternal and female sexual behavior require priming with gonadal steroids (Pedersen and Prange, 1979;Fahrbach et al, 1984;Caldwell et al, 1986;Gorzalka and Lester, 1987;Kendrick et al, 1987). At a cellular level, estrogen increases the hypothalamic synthesis of OT (Caldwell et al, 1989; but see also Burbach et al, 1990) and induces oxytocin receptors in discrete limbic nuclei (De Kloet et al, 1986;Insel, 1986;Coirini et al, 1989;Tribollet et al, 1990). Physiologic concentrations of estrogen appear sufficient to induce production of functional OT receptors (Insel, 1986;Pliskin et al, 1989).…”