Human membrane-associated neutral endopeptidase
(NEP; EC 3.4.24.11 ), encodes a 100-kD type II transmembrane glycoprotein, is also known as enkephalinase. NEP cleaves peptides at the amino side of hydrophobic residues
and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and
bradykinin.
General function
Hydrolase, Peptidase/Protease
Comment
Cellular localization
Secreted, Plasma membrane
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization
Granulosa
Comment
Zappulla JP, et al reported that
neutral endopeptidase is
expressed on the follicular granulosa
cells of rabbit ovaries.
Neutral endopeptidase (NEP) is a zinc metallopeptidase
ubiquitously distributed
in various tissues in mammals. This peptidase is involved in
the post-secretory
metabolism of various neuropeptides and peptide hormones in
vivo, such as
enkephalins, bradykinin, atrial natriuretic peptide,
substance P and endothelins. In
this paper the authors show that NEP is expressed in ovaries as a
110-kDa glycosylated
integral membrane protein with enzymatic properties similar
to those of the
kidney protein. Using immunohistochemistry, they localize the
peptidase in the
granulosa cells of follicles at all stages of maturation,
with the exception of
atretic follicles. They also observe immunoreactive staining
in the epithelia that
lines the blood vessels in the medulla and the surface of
the ovary.
Follicle stages
Secondary, Antral, Preovulatory
Comment
Gonadotropin Stimulation Increases the Expression of Angiotensin-(1-7) and Mas Receptor in the Rat Ovary. Pereira VM et al. We have previously shown the presence of immunoreactive angiotensin-(1-7) [Ang-(1-7)] in rat ovary homogenate and its stimulatory effect on estradiol and progesterone production in vitro. In the current study, we investigated the presence and cellular distribution of Ang-(1-7) and the Mas receptor, the expression of Mas and angiotensin-converting enzyme 2 (ACE2) messenger RNA (mRNA), and the enzymatic activity in the rat ovary following gonadotropin stimulation in vivo. Immature female Wistar rats (25 days old) were injected subcutaneously (SC) with equine chorionic gonadotropin (eCG, 20 IU in 0.2 mL) or vehicle 48 hours before euthanasia. Tissue distributions of Ang-(1-7), Mas receptor, and ACE2 were evaluated by immunohistochemistry, along with angiotensin II (Ang II) localization, while the mRNA expression levels of Mas receptor and ACE2 were evaluated by real-time polymerase chain reaction (PCR). In addition, we determined the activity of neutral endopeptidase (NEP), prolyl endopeptidase (PEP), and ACE by fluorometric assays. After eCG treatment, we found strong immunoreactivity for Ang-(1-7) and Mas primarily in the theca-interstitial cells, while Ang II appeared in the granulosa but not in the thecal layer. Equine chorionic gonadotropin treatment increased Mas and ACE2 mRNA expression compared with control animals (3.3- and 2.1-fold increase, respectively; P < .05). Angiotensin-converting enzyme and NEP activities were lower, while PEP activity was higher in the eCG-treated rats (P < .05). These data show gonadotropin-induced changes in the ovarian expression of Ang-(1-7), Mas receptor, and ACE2. These findings suggest that the renin-angiotensin system (RAS) branch formed by ACE2/Ang-(1-7)/Mas, fully expressed in the rat ovary and regulated by gonadotropic hormones, could play a role in the ovarian physiology.