TY - JOUR
T1 - Neuregulins signaling via a glial erbB-2-erbB-4 receptor complex contribute to the neuroendocrine control of mammalian sexual development
AU - Ma, Ying J.
AU - Hill, Diane F.
AU - Creswick, Kimberly E.
AU - Costa, Maria E.
AU - Cornea, Anda
AU - Lioubin, Mario N.
AU - Plowman, Gregory D.
AU - Ojeda, Sergio R.
PY - 1999/11/15
Y1 - 1999/11/15
N2 - Activation of erbB-1 receptors by glial TGFα has been shown to be a component of the developmental program by which the neuroendocrine brain controls mammalian sexual development. The participation of other members of the erbB family may be required, however, for full signaling capacity. Here, we show that activation of astrocytic erbB-2/erbB-4 receptors plays a significant role in the process by which the hypothalamus controls the advent of mammalian sexual maturation. Hypothalamic astrocytes express both the erbB-2 and erbB-4 genes, but no erbB-3, and respond to neuregulins (NRGs) by releasing prostaglandin E2 (PGE2), which acts on neurosecretory neurons to stimulate secretion of luteinizing hormone-releasing hormone (LHRH), the neuropeptide controlling sexual development. The actions of TGFα and NRGs in glia are synergistic and involve recruitment of erbB-2 as a coreceptor, via erbB-1 and erbB-4, respectively. Hypothalamic expression of both erbB-2 and erbB-4 increases first in a gonad-independent manner before the onset of puberty, and then, at the time of puberty, in a sex steroid-dependent manner. Disruption of erbB-2 synthesis in hypothalamic astrocytes by treatment with an antisense oligodeoxynucleotide inhibited the astrocytic response to NRGs and, to a lesser extent, that to TGFα and blocked the erbB-dependent, glia- mediated, stimulation of LHRH release. Intracerebral administration of the oligodeoxynucleotide to developing animals delayed the initiation of puberty. Thus, activation of the erbB-2-erbB-4 receptor complex appears to be a critical component of the signaling process by which astrocytes facilitate the acquisition of female reproductive capacity in mammals.
AB - Activation of erbB-1 receptors by glial TGFα has been shown to be a component of the developmental program by which the neuroendocrine brain controls mammalian sexual development. The participation of other members of the erbB family may be required, however, for full signaling capacity. Here, we show that activation of astrocytic erbB-2/erbB-4 receptors plays a significant role in the process by which the hypothalamus controls the advent of mammalian sexual maturation. Hypothalamic astrocytes express both the erbB-2 and erbB-4 genes, but no erbB-3, and respond to neuregulins (NRGs) by releasing prostaglandin E2 (PGE2), which acts on neurosecretory neurons to stimulate secretion of luteinizing hormone-releasing hormone (LHRH), the neuropeptide controlling sexual development. The actions of TGFα and NRGs in glia are synergistic and involve recruitment of erbB-2 as a coreceptor, via erbB-1 and erbB-4, respectively. Hypothalamic expression of both erbB-2 and erbB-4 increases first in a gonad-independent manner before the onset of puberty, and then, at the time of puberty, in a sex steroid-dependent manner. Disruption of erbB-2 synthesis in hypothalamic astrocytes by treatment with an antisense oligodeoxynucleotide inhibited the astrocytic response to NRGs and, to a lesser extent, that to TGFα and blocked the erbB-dependent, glia- mediated, stimulation of LHRH release. Intracerebral administration of the oligodeoxynucleotide to developing animals delayed the initiation of puberty. Thus, activation of the erbB-2-erbB-4 receptor complex appears to be a critical component of the signaling process by which astrocytes facilitate the acquisition of female reproductive capacity in mammals.
KW - Astroglial cells
KW - Female sexual development
KW - Glial growth factors
KW - Hypothalamus
KW - Puberty
KW - Tyrosine kinase receptors
UR - http://www.scopus.com/inward/record.url?scp=0033571858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033571858&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.19-22-09913.1999
DO - 10.1523/jneurosci.19-22-09913.1999
M3 - Article
C2 - 10559400
AN - SCOPUS:0033571858
SN - 0270-6474
VL - 19
SP - 9913
EP - 9927
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 22
ER -