Effects of the purine biosynthesis pathway inhibitors azaserine, hadacidin, and mycophenolic acid on the developing ovine corpus luteum.
De novo synthesis precursors of the purine second messengers adenosine, guanosine and inosine are adenosine, guanosine and inosine monophosphate (AMP, GMP, IMP), respectively. Inhibitors of the de novo purinergic synthesis pathways for AMP, GMP and IMP by hadacidin, mycophenolic acid and azaserine, respectively, or adenosine, guanosine or inosine alone or in combination were given every 4 or 6 hours in vivo. Treatments were given into the ovarian vascular pedicle sheath adjacent to the luteal-bearing ovary in three separate experiments to determine whether purines were involved in development of the corpus luteum. Hadacidin lowered AMP (p < or = 0.01) and azaserine tended to lower IMP and the GMP: AMP ratio (p < or = 01) while mycophenolic acid tended to lower the GMP:AMP ratio (p < or = 0.1) in luteal tissue. Azaserine (150 mg) increased progesterone (p < or = 0.01) on some days but guanosine or inosine had no effect on profiles of progesterone in jugular blood of the developing corpus luteum (p > or = 0.1). Azaserine (500 micrograms) tended to lower progesterone in jugular blood (p < or = 0.1) while profiles of progesterone did not differ among guanosine or inosine or adenosine, guanosine and inosine plus hadacidin, mycophenolic acid and azaserine treatment groups compared to controls (p > or = 0.1). Weights of corpora lutea or composition of cell types in the corpus luteum or their viability were not affected by adenosine, guanosine, inosine, hadacidin, mycophenolic acid or azaserine (p > or = 0.1). Since profiles of jugular progesterone did not differ between treatments during development of the corpus luteum, these results suggest that progesterone production by the developing corpus luteum is a) less dependent on de novo synthesized purines or b) there may be a non-purinergic-dependent second messenger system controlling biosynthesis of steroids in the developing ovine corpus luteum.
Miller-Patrick
K
K
Department of Animal Sciences, University of Hawaii at Manoa 96822.
Vincent
D L
DL
Early
R J
RJ
Weems
Y S
YS
Tanaka
Y
Y
Ashimine
D T
DT
Nusser
K D
KD
Lee
C N
CN
Ledgerwood
K S
KS
Weems
C W
CW
D000249:Adenosine Monophosphate / Q000096:biosynthesis; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D001377:Azaserine / Q000493:pharmacokinetics / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D004971:Estrus / Q000502:physiology; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000096:biosynthesis; D007291:Inosine Monophosphate / Q000096:biosynthesis; D009173:Mycophenolic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis; D011687:Purines / Q000378:metabolism*; D011863:Radioimmunoassay; D012756:Sheep
D000903:Antibiotics, Antineoplastic; D011687:Purines; D007291:Inosine Monophosphate; D000249:Adenosine Monophosphate; D011374:Progesterone; D006157:Guanosine Monophosphate; D001377:Azaserine; C001321:hadacidin; D009173:Mycophenolic Acid; D005998:Glycine