Tissue Kallikrein in Rat Brain and Pituitary: Regional Distribution and Estrogen Induction in the Anterior Pituitary*

Abstract

We have detected tissue kallikrein and kallikrein mRNA in various brain regions with a kallikrein direct RIA and with nucleic acid hybridization using a kallikrein cDNA probe. In the direct RIA, rat urinary kallikrein-like activity was found in the pituitary and pineal glands, hypothalamus, cerebral cortex, cerebellum, and brain stem. Pituitary and pineal gland kallikrein concentrations were significantly higher than those in other regions. Only in pituitary was there a significant difference in tissue kallikrein concentration according to sex, with glands from female rats showing levels 4-fold higher than those from male rats. Kallikrein mRNAs were detected in all of the regions and were about 4-fold higher in female than in male pituitary gland. Northern blot analyses show sex dimorphism of pituitary kallikrein mRNA, similar in size to submandibular gland and kidney mRNA. In castrated male rats, whole pituitary kallikrein content was reduced to 50% of the control value and increased 1.7-fold with testosterone replacement and 18-fold with 17 beta-estradiol treatment. Neither T4 nor cortisol affected whole pituitary kallikrein levels in the castrated male rat, but testosterone decreased pituitary kallikrein in normal female rats by 35%. When anterior pituitary or neurointermediate lobe extracts were separately examined, immunoreactive kallikrein was 10.2- and 1.3-fold higher respectively, in female than in male rat lobes. Estradiol benzoate (30 micrograms/kg) administration increased kallikrein levels 90- and 22-fold, respectively, in the anterior pituitary of gonadectomized male and female rats, while it increased by only 40-50% kallikrein levels in the male and female neurointermediate lobe. In dot blot analysis, kallikrein mRNA levels were increased 5-fold by 17 beta-estradiol in the whole pituitary of castrated male rats. In the cytoplasmic dot hybridization analysis, estradiol benzoate treatment increased kallikrein mRNA levels 54-fold in the anterior pituitary of ovariectomized rats. The data show that a tissue kallikrein indistinguishable thus far from a urinary kallikrein is widely distributed in brain and pituitary and that levels of enzyme and mRNA are comparable in certain central sites. Kallikrein levels in the anterior and neurointermediate pituitaries are differentially regulated by estrogen.

Identification, purification, and localization of tissue kallikrein in rat heart

“…Many tissue sites, not previously recognized as kallikrein-containing, have been found to have a proteinase that is enzymically and immunologically identical with the tissue kallikrein in urine, kidney and salivary gland. These sites include spleen , vasculature (Nolly et al, 1985), pituitary (Powers & Hatala, 1986;Chao et al, 1987), brain and skeletal muscle (Shimojo et al, 1987). In addition to kininogen, recent studies have expanded the list of potential natural substrates to include apolipoprotein B-100 (Cardin et al, 1984), renin (Sealey et al, 1978), insulin (ole-MoiYoi et al, 1979) and pro-(atrial natriuretic peptide) (pro-ANP) (Currie et al, 1984).…”

Rhythmic Expression of Adenylyl Cyclase VI Contributes to the Differential Regulation of Serotonin N-Acetyltransferase by Bradykinin in Rat Pineal Glands

“…The kallikrein-kinin system has been identified in the mammalian nervous system (12,13). Interestingly, kallikrein mRNA and enzyme activity are higher in the rat pineal gland than other brain regions (14,15). Consistent with this finding, immunoelectron microscopy data by Kudo et al (16) disclosed that kallikrein is localized in perivascular spaces in the rat pineal gland.…”

The Kallikrein-Kinin System as a Regulator of Cardiovascular and Renal Function

“…While the kallikrein gene is expressed mainly in the submandibular gland, pancreas and kidney, we detected small amounts of kallikrein mRNA in the heart, vascular tissue, and adrenal glands on polymerase chain reaction (PCR) (189,237). Kallikrein and similar enzymes have been found in the arteries and veins (190), heart (188), brain (58), spleen (57), adrenal glands (255), and blood cells (189); they have also been observed in the pituitary gland (66,216), pancreas (84), large and small intestines (242,320), and salivary and sweat glands (106) along with their exocrine secretions. Some of these enzymes were probably true kallikrein, while others may represent separate members of the kallikrein family.…”