Progesterone production and actions in the human central nervous system and neurogenic tumors.
Progesterone has been suggested to be involved in the functions of the nervous system, but it has yet to be examined in humans. Progesterone has also been postulated to be involved in the biological behavior of various human neurogenic tumors via progesterone receptors A and B (PR-A and PR-B). In this study we examined the expression of PR and the enzymes responsible for progesterone biosynthesis (P450scc, 3betahydroxysteroid dehydrogenase, and steroidogenic acute regulatory protein) in human brain. We also examined the distribution of PR isoforms in neurogenic tumors using immunohistochemistry and RT-PCR analysis. The presence of PR and mRNA for P450scc, 3beta-hydroxysteroid dehydrogenase, and steroidogenic acute regulatory protein was detected in human brain. PR isoforms were detected in neurogenic tumors. PR-A and PR-B were equally expressed in meningiomas, but PR-B was the predominant isoform compared with PR-A in astrocytic tumors and Schwannomas. There was a statistically significant inverse correlation between PR-A and the proliferation index in meningiomas and astrocytic tumors. These findings suggest that progesterone is locally synthesized and exerts its actions through PR in the human central nervous system, and that progesterone may be involved in regulation of the growth and development of neurogenic tumors via PR, especially in the inhibition of tumor cell proliferation via PR-A.
Inoue
Tsukasa
T
Department of Pathology, Second Department of Surgery, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. tsukasai@gonryo.med.tohoku.ac.jp
Akahira
Jun-Ichi
J
Suzuki
Takashi
T
Darnel
Andrew D
AD
Kaneko
Chika
C
Takahashi
Kazuhiro
K
Hatori
Masahito
M
Shirane
Reizo
R
Kumabe
Toshihiro
T
Kurokawa
Yoshimochi
Y
Satomi
Susumu
S
Sasano
Hironobu
H
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000378:metabolism*; D002648:Child; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008579:Meningioma / Q000378:metabolism; D008875:Middle Aged; D009442:Neurilemmoma / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics; D011374:Progesterone / Q000096:biosynthesis* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme