Abstract
The pars tuberalis (PT) region of the anterior pituitary plays a physiological role in seasonal animals. The primary signal transduction mechanism of the melatonin receptor in this tissue is an inhibition of cAMP signaling. However, nothing is known about the endocrine signals that activate cAMP synthesis in the cells of the PT, as previous studies relied on the pharmacological tool, forskolin, to stimulate cAMP synthesis. Here we show that pituitary adenylate cyclase-activating polypeptide (PACAP) activates cAMP synthesis in the cells of the PT. The pharmacology of cAMP activation by PACAP peptides suggests that cAMP activation is mediated by the type I PACAP receptor. PACAP treatment of PT cells results in cellular responses that are consistent with cAMP activation in these cells, including activation of MAPK and elevation of melatonin receptor mt1 mRNA expression. These responses can be inhibited by melatonin, demonstrating that activation of cAMP occurs within the melatonin-responsive cells. However, although PACAP activates cAMP in the cells of the PT, the effect of PACAP may not be direct, as colocalization in situ hybridization studies demonstrates that the type I PACAP receptor and the melatonin mt1 receptor do not colocalize on the cells of the PT.
| Original language | English |
|---|---|
| Pages (from-to) | 2366-2375 |
| Number of pages | 10 |
| Journal | Endocrinology |
| Volume | 143 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2002 |
Keywords
- vasoactive intestinal polypeptide
- hypophyseal portal blood
- cyclic-amp accumulation
- hypothalamic peptide
- protein-kinase
- rat pituitary
- in-vitro
- receptors
- PACAP
- sheep
Cite this
Pituitary adenylate cyclase-activating polypeptide acts as a paracrine regulator of melatonin-responsive cells of the ovine pars tuberalis. / Barrett, Perry; Messager, S ; Schuster, C ; Moar, Kim-Marie; Mercer, Julian; Morgan, Peter John.
In: Endocrinology, Vol. 143, No. 6, 06.2002, p. 2366-2375.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pituitary adenylate cyclase-activating polypeptide acts as a paracrine regulator of melatonin-responsive cells of the ovine pars tuberalis
AU - Barrett, Perry
AU - Messager, S
AU - Schuster, C
AU - Moar, Kim-Marie
AU - Mercer, Julian
AU - Morgan, Peter John
PY - 2002/6
Y1 - 2002/6
N2 - The pars tuberalis (PT) region of the anterior pituitary plays a physiological role in seasonal animals. The primary signal transduction mechanism of the melatonin receptor in this tissue is an inhibition of cAMP signaling. However, nothing is known about the endocrine signals that activate cAMP synthesis in the cells of the PT, as previous studies relied on the pharmacological tool, forskolin, to stimulate cAMP synthesis. Here we show that pituitary adenylate cyclase-activating polypeptide (PACAP) activates cAMP synthesis in the cells of the PT. The pharmacology of cAMP activation by PACAP peptides suggests that cAMP activation is mediated by the type I PACAP receptor. PACAP treatment of PT cells results in cellular responses that are consistent with cAMP activation in these cells, including activation of MAPK and elevation of melatonin receptor mt1 mRNA expression. These responses can be inhibited by melatonin, demonstrating that activation of cAMP occurs within the melatonin-responsive cells. However, although PACAP activates cAMP in the cells of the PT, the effect of PACAP may not be direct, as colocalization in situ hybridization studies demonstrates that the type I PACAP receptor and the melatonin mt1 receptor do not colocalize on the cells of the PT.
AB - The pars tuberalis (PT) region of the anterior pituitary plays a physiological role in seasonal animals. The primary signal transduction mechanism of the melatonin receptor in this tissue is an inhibition of cAMP signaling. However, nothing is known about the endocrine signals that activate cAMP synthesis in the cells of the PT, as previous studies relied on the pharmacological tool, forskolin, to stimulate cAMP synthesis. Here we show that pituitary adenylate cyclase-activating polypeptide (PACAP) activates cAMP synthesis in the cells of the PT. The pharmacology of cAMP activation by PACAP peptides suggests that cAMP activation is mediated by the type I PACAP receptor. PACAP treatment of PT cells results in cellular responses that are consistent with cAMP activation in these cells, including activation of MAPK and elevation of melatonin receptor mt1 mRNA expression. These responses can be inhibited by melatonin, demonstrating that activation of cAMP occurs within the melatonin-responsive cells. However, although PACAP activates cAMP in the cells of the PT, the effect of PACAP may not be direct, as colocalization in situ hybridization studies demonstrates that the type I PACAP receptor and the melatonin mt1 receptor do not colocalize on the cells of the PT.
KW - vasoactive intestinal polypeptide
KW - hypophyseal portal blood
KW - cyclic-amp accumulation
KW - hypothalamic peptide
KW - protein-kinase
KW - rat pituitary
KW - in-vitro
KW - receptors
KW - PACAP
KW - sheep
U2 - 10.1210/en.143.6.2366
DO - 10.1210/en.143.6.2366
M3 - Article
VL - 143
SP - 2366
EP - 2375
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 6
ER -