Daisy L. Daubert

Angiotensin II : a reproductive hormone too?

It has long been known that angiotensin II (Ang II) can affect reproductive tissues such as the uterus. However, the existence of a local renin-angiotensin system (RAS) in female as well as male reproductive tissues is a relatively recent observation. Of great interest is the discovery that all components of the RAS are present in the ovary, that the ovary secretes components of the RAS into the bloodstream, and that the ovary itself is responsive to Ang II. Recent studies suggest that the primary role of Ang II in the ovary is to cause atresia in non-ovulatory follicles; however, there is also compelling data to suggest that Ang II facilitates ovulation. Male reproductive structures also contain all of the components of the RAS, gonadotropins regulate the activity of these components, and these tissues have Ang II receptors. Of great interest is the expression of testis-specific angiotensin-converting enzyme (ACE), which is located on germ cells. Recent studies using gene knock-out techniques indicate that testis ACE plays an important role in male fertility. However, the overall significance of the RAS for normal reproductive function remains questionable. There is now a body of evidence implicating the RAS in pathophysiologies associated with reproductive function, which gives rise to the possibility that drugs acting on the RAS might ameliorate some of these disorders. Considerable work remains to determine the role of Ang II in reproductive functions.

Changes in angiotensin II receptors in dopamine-rich regions of the mouse brain with age and ethanol consumption

The density of angiotensin II (Ang II) receptors was determined in three dopaminergic nerve terminal-rich brain regions (caudate putamen, nucleus accumbens, and ventral pallidum) of mice that were given either water (control) or 20% w/v ethanol (EtOH) to drink for either 2-8 weeks (young) or 46 weeks (old). The receptors were labeled with 125I-sarcosine1, isoleucine8 angiotensin II (125I-SI Ang II) and measured by quantitative densitometric image analysis (receptor autoradiography) or by saturation binding assays on homogenates of these brain regions. The selective AT2 receptor subtype antagonist PD 123319 (10 microM) was used to inhibit 125I-SI Ang II binding to AT2 receptors to determine AT1 receptor density in brain sections. In young control mice the density of Ang II receptor binding sites in the caudate putamen was 407+/-26 fmol/g, in the nucleus accumbens the density was 346+/-27 fmol/g, and in the ventral pallidum the density was 317+/-27 fmol/g. Less than 5% of specific 125I-SI Ang II binding was displaced by PD 123319, suggesting that nearly all of the Ang II receptors in these brain regions were the AT1 subtype. The Bmax in homogenates of these three regions in young control mice was 11.0+/-2.1 fmol/mg protein. The KD was 0.49+/-0.13. Ang II receptors in old mouse brains were decreased, respectively, by 32%, 35% and 30% in the caudate putamen, nucleus accumbens and ventral pallidum (p<0.001). Ang II receptors were slightly, but not significantly increased in both young and old EtOH-consuming mice.

Angiotensin II increases intracellular calcium concentration in pig endometrial stromal cells through type 1 angiotensin receptors, but does not stimulate phospholipase C activity or prostaglandin F2α secretion

Although the presence of endometrial receptors for angiotensin (Ang) II has been demonstrated, a specific function for AngII in the uterus has not been identified. Cytosolic free Ca2+ concentration [Ca2+]i, phospholipase C (PLC) activity and prostaglandin (PG) F2alpha secretion in response to AngII and oxytocin (OT) were measured in pig endometrial stromal cells collected 16 days after oestrus. Treatment with 100 nM OT or AngII increased (P<0.001) [Ca2+]i in stromal cells similarly (720 +/- 34 v. 690 +/- 33 pM, respectively). Subsequent administration of OT or AngII to the same cells induced smaller [Ca2+]i increases (25% or 35% of the initial responses, respectively) that occurred only if the second exposure to the same agent took place at least 5 min after the first. When administered sequentially, OT and AngII each induced a full response within 1 min of the previous treatment, regardless of which peptide was applied first. Whereas OT increased PLC activity and PGF2alpha secretion in stromal cells (P<0.01), AngII did not increase either PLC activity or PGF2alpha secretion. Type I AngII (AT1) receptors were present on stromal cells, whereas AT2 receptors were absent. Therefore, the effect of AngII in stromal cells was mediated via AT1 receptors. That AngII increased [Ca2+]i in stromal cells, but did not increase PLC or PGF2alpha secretion, indicates that either AngII releases a pool of Ca2+ through a mechanism that is not mediated by PLC and is not involved in PGF2alpha secretion or that a mechanism for PGF2alpha production other than one involving Ca2+ may exist.