Type 1 angiotensin II (ANG II) receptors play crucial roles in the regulation of blood pressure and fluid osmolarity, whereas the physiological roles of type 2 ANG II receptors (AT2) remain unclear. Because AT2 is expressed in atretic follicles where granulosa cells undergo apoptosis, we examined the space and time relationship between AT2 expression and follicle atresia in vivo and the effect of AT2 on follicle-stimulating hormone (FSH) actions in vitro. Binding studies, autoradiography, and RT-PCR of AT2 revealed that the AT2 content in granulosa cells was time dependently increased at both protein and mRNA levels in equine chorionic gonadotropin-treated immature female rats. This increase paralleled the progression of atresia. ANG II suppressed FSH-caused prevention of DNA fragmentation, increases in luteinizing hormone receptor content, and estrogen production through AT2 in cultured granulosa cells. Moreover, FSH-induced stimulation of extracellular signal-regulated kinase activity, critical for cell survival, was inhibited by AT2 stimulation. These results suggest that AT2 mediates the progression of follicle atresia through granulosa cell apoptosis by inhibiting FSH actions.

Abstract. Nishiyama Y, Nejima J, Watanabe A, Kotani E, Sakai N, Hatamochi A, Shinkai H, Kiuchi K, Tamura K, Shimada T, Takano T, Katayama Y (Nippon Medical School, Tokyo, and Chiba University School of Medicine, Chiba, Japan). Ehlers±Danlos syndrome type IV with a unique point mutation in COL3 A1 and familial phenotype of myocardial infarction without organic coronary stenosis (Case Report). J Intern Med 2001; 249: 103±108.We report on a 43-year-old male patient with Ehlers± Danlos syndrome (EDS) type IV with acute myocardial infarction (MI) without organic coronary stenosis. The disease was complicated with pneumothorax, subcutaneous and mediastinal emphysema, and splenic artery rupture. Three of the patient's family members suffered sudden cardiac death or MI. A diagnosis of EDS type IV was confirmed by decreased production of type III collagen by 86%. Mutation analysis revealed a point mutation in the COL3A1 gene that substituted glycine for aspartate at amino acid position 877. This mutation had not been reported as pathogenic for EDS type IV. These findings suggest close linkage between the mutation and the phenotype with familial MI.

The purpose of this study was to detect the presence of mRNA encoding pituitary adenylate cyclase-activating polypeptide (PACAP) (10, 100 and 1000 ng ml \m=-\ 1). At the end of the incubation period, the incubation media were collected and concentrations of progesterone, 20\g=a\-hydroxypregn-4-en-3-one (20\g=a\-OH-P)H-P) and cAMP were measured. Increasing concentrations of significantly stimulated the production of progestins (progesterone and 20\g=a\-OH-P) and cAMP accumulation in a dose-dependent manner (P < 0.01; ANOVA). This effect was observed in media cultured for 24 and 48 h in both basal and LH-stimulated states. PACAP-38 did not significantly affect the ratio of progesterone: 20\g=a\-OH-P produced by granulosa cells cultured for 24 h in the LH-stimulated state. However, at 1000 ng ml \m=-\1, PACAP-38 significantly decreased the ratio of progesterone to 20\g=a\-OH-P production in granulosa cells cultured for 48 h (P < 0.01). These results suggest that granulosa cells from rat ovary express mRNA encoding PACAP type IA receptor and that PACAP may regulate granulosa cell differentiation and play an important role in the reproductive process. IntroductionPituitary adenylate cyclase-activating polypeptide (PACAP) was first isolated from ovine hypothalamus by its potent activity to stimulate cAMP production in rat anterior pituitary cells (Miyata et al, 1989). PACAP is a novel member of the secretin-glucagon-vasoactive intestinal polypeptide (VIP)-growth hormone releasing hormone (GHRH) family of peptides (Arimura, 1992). The 28 amino terminal residues of PACAP show 68% similarity to VIP. Six amino terminal residues of PACAP are identical to residues in GHRH (Miyata et al, 1989). PACAP occurs as two biologically active, amidated forms, (Miyata et al, 1990). Since its isolation, many studies have described PACAP activity in a variety of tissues (Arimura, 1992; Rawlings and Hezareh, 1996). Although the hypothalamus contains the highest concentration of PACAP, the testes also contain significant amounts. In fact, the total PACAP content of both testes is approximately twice that of the total PACAP content of the extrahypothalamic areas of the brain (Arimura et al, 1991). In the testes and epididymides, PACAP type I receptors are localized to Sertoli cells (Heindel et al, 1992) and the tails of spermatozoa (Shivers et al, 1991). mRNA encoding PACAP is also expressed in rat testes (Kononen et al, 1994

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