Gonadotropin-releasing hormone-Cu complex (Cu-GnRH) transcriptional activity in vivo in the female rat anterior pituitary gland

Autor: Alina Gajewska, Grzegorz Kotarba, Katarzyna Biernacka, Marlena Zielińska-Górska
Rok vydání: 2020
Předmět:
0301 basic medicine
endocrine system
medicine.medical_specialty
medicine.drug_class
Gene Expression
Nitric Oxide Synthase Type I
Gonadotropin-releasing hormone
Steroidogenic Factor 1
Gonadotropic cell
Gonadotropin-Releasing Hormone
03 medical and health sciences
0302 clinical medicine
Anterior pituitary
Pituitary Gland
Anterior
In vivo
Internal medicine
medicine
Animals
RNA
Messenger
Rats
Wistar
Early Growth Response Protein 1
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
Messenger RNA
Chemistry
General Neuroscience
Luteinizing Hormone
Receptor antagonist
Rats
PRKACA
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Gene Expression Regulation
Pituitary Adenylate Cyclase-Activating Polypeptide
Female
Luteinizing hormone
Copper
Receptors
LHRH
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Zdroj: Brain Research Bulletin. 156:67-75
ISSN: 0361-9230
Popis: Unlike gonadotropin-releasing hormone (GnRH) analogues characterized by amino acid replacement in decapeptide primary structure, Cu-GnRH molecule preserves the native sequence but contains a Cu2+ ion stably bound to the nitrogen atoms including that of the imidazole ring of His2. Cu-GnRH can operate via cAMP/PKA signalling in anterior pituitary cells, suggesting that it may affect selected gonadotropic network gene transcription in vivo. We analysed pituitary mRNA expression of Egr-1, Nr5a1, and Lhb based on their role in luteinizing hormone (LH) synthesis; and Nos1, Adcyap1, and Prkaca due to their dependence on cAMP/PKA activity. In two independent experiments, ovariectomized rats received intracerebroventricular pulsatile (one pulse/h or two pulses/h over 5 h) microinjections of 2 nM Cu-GnRH; 2 nM antide (GnRH antagonist) + 2 nM Cu-GnRH; 100 nM PACAP6–38 (PACAP receptor antagonist) + 2 nM Cu-GnRH. Relative expression of selected mRNAs was determined by qRT-PCR. LH serum concentration was examined according to RIA. All examined genes responded to Cu-GnRH stimulation with increased transcriptional activity in a manner dependent on pulse frequency pattern. Increased expression of Nr5a1, Lhb, Nos1, Adcyap1, and Prkaca mRNA was observed solely in rats receiving the complex with frequency of two pulses/h over 5 h. Egr-1 transcription was up-regulated for both applied Cu-GnRH pulsatile patterns. The stimulatory effect of Cu-GnRH on gene transcription was dependent on both GnRH receptor and PAC-1 activation. In conclusion, obtained results indicate that Cu-GnRH complex is a GnRH analogue able to induce both IP3/PKC and cAMP/PKA-dependent gonadotrope network gene transcription in vivo.
Databáze: OpenAIRE
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