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Pancreatic Polypeptide Immunoreactive Cells and Nerves in the Canine Pituitary

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Pancreatic Polypeptide Immunoreactive Cells and Nerves in the Canine Pituitary Biomedical Research 3 (5) 525-533, 1982 PANCREATIC POLYPEPTIDE IMMUNOREACTIVE CELLS AND NERVES IN THE CANINE PITUITARY SHIGEKI FUJII‘, SHIGEAKI BABA1 and TUNEO FUJITA2 1The Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650, and ZDepart~ merit of Anatomy, Niigata University School of Medicine, Niigata 951, Japan ABSTRACT . Pancreatic polypeptide (PP)-like immunoreactivity was found to occur in the canine pituitary. Numerous PP-immunoreactive cells were observed in the pars intermedia and a few cells were scattered in the pars tuberalis. Studies using the anti-C terminal fragment of adrenocorticotropic hormone (ACTH) serum suggested the presence of three cell types in the pars intermedia; one type having both PP- and ACTH-like immunoreactivity was predominant, a second type possessing only ACTH-like im- munoreactivity appeared in small clusters, and a third type, which did not react to either antiserum, was seen in small numbers among the other type cells. In the pars tuberalis, only cells with a strong ACTH-like immunoreactivity showed PP-like immunoreactivity, while weakly stained cells did not. In the pars distails, almost no PP-like immunoreactivity was detected, although numerous ACTH-immunoreactive cells were observed. PP-immunoreactive nerve fibers were mainly observed in the hypothalamus and the infundibulum. In the pituitary of canine fetuses, ACTH-like immunoreactivity was observed, but a PP-like substance could not be detected. Some pituitary hormones and their chemically most representative gut hormones, is present in related peptides have been demonstrated in the a group of cells containing ACTH and Ot- gastro-entero-pancreatic (GEP) tissues by im- melanocyte-stimulating hormone (06-MSH) in munohistochemistry and radioimmunoassay. the mammalian pituitaries (l9, 30). Adrenocorticotropic hormone (ACTH)-like im- We have investigated the morphological munoreactivity has been reported in gastrin- features of PP cells in the GEP endocrine system secreting cells localized in the antropyloric and other neuroendocrine systems. This paper mucosa and in both gastrin and pancreatic will deal with the immunohistochemical and polypeptide (PP) cells in the pancreas (ll“l8). morphological aspects of the PP-immunoreac- These findings were followed by the observations tive cells and nerves in the canine pituitary that growth hormone-like immunoreactivity gland. occurred in the antral gastrin cells and in the pancreatic endocrine cells distributed along the MATERIALS AND METHODS islet periphery in several mammalian species in- Tissue ll/laterials cluding humans (6, 28). Furthermore, )3- endorphin- and leu-enkephalin-like immunoreac- Eight. adult dogs (3 males and 5 females, body tivities were identified in the pancreatic endocrine weight: 9-ll kg) which were kept in individual cells (5, 31) and in enterochromafiin cells in the kennels and given a standard diet (Lovely*R‘, gut (1), respectively. Oriental Yeast, Tokyo) and tap water ad I1'bi'tum Conversely, recent immunohistochemical were sacrificed by exsanguination under sodium studies have revealed that gastrin, one of the thioamylal intravenous anesthesia at a fixed time 526 S. FUJII, S. BABA and T. FUJITA (from 10:00 to ll:00 a.m.). Eight pituitaries Sra1'm'ng Conrrols with a part of the hypothalamus and the pan- creata were removed as quickly as possible and The specificities of antisera were histologically fixed by immersion in Bouin’s fluid for 12 h at identified by the following methods: 1) normal room temperature. Three fetuses 5-6 cm in non-immunized rabbit serum (NRS, 0.5 %, crown-rump length were taken from an anesthe- DAKO-immunoglobulins) or phosphate buffer tized dog and fixed whole for 24h in Bouin’s saline (PBS, 0.01 M, pH 7.2) was utilized as the fluid. After dehydration and embedding in substituting primary antibody for anti-BPP parafiin, ordinary sections of pituitaries, fetal serum; and 2) immunoabsorption tests of anti- heads (both sagitally), and pancreata were cut BPP serum (diluted 1:2,000) and anti-porcine at 4 ,um. Adjacent sections of 2 pm thickness ACTH serum (1 : 500) incubated for 24 h at 4°C were cut from the pituitary. prior to staining with the following peptides (100 /zg per ml diluted anti-serum): BPP, porcine PP(PPP), synthetic bovine CLIP and synthetic Immimo/1is2‘0c/iemisrry m-MSH. The former two peptides were donated Anti-bovine pancreatic polypeptide (BPP) rabbit by Dr Chance and the latter two were provided serum kindly donated by Dr R. E. Chance, Lilly by Professor Haruaki Yajima, Faculty of Research Laboratories, Eli Lilly, Indianapolis, Pharmaceutical Sciences, Kyoto University, IN, U.S.A. (Lot. 615-R1 10-146-10) was used in a Kyoto, Japan. dilution of 1 : 2,000. Anti-porcine ACTH rabbit serum kindly donated by Dr Yukio Hirata, RESULTS Third Division, Department of Medicine, Kobe University School of Medicine, was fully cross- Marked PP-like immunoreactivity occurred in all reacted with corticotropin-like intermediate lobe the pituitaries of the adult dogs examined. peptide (CLIP) and COOH-terminal fragment of In the adenohypophysis, numerous PP-im- ACTH, but not with other related peptides such munoreactive cells were gathered in the pars as 06-MSH, )3-lipotropin ([3-LPH), or fl-endor- intermedia. The PP-positive cells showed a phine. This antiserum was diluted 1:500 for preferential distribution within the pars inter- use. Both sera, prior to use, were incubated for media. In the lower portion of the pars inter- 30 min at 56°C to inactivate the complements media under the pars nervosa, the immunoreac- possibly contained. tivity was displayed in the great majority of Deparaffinized sections were treated first with endocrine cells (over 95 percent) (Fig. 1), but 3% H202 solution in order to destroy any PP-positive cells were fewer in the upper portion endogenous peroxidase activity, followed by of the pars intermedia extending over the incubation with 0.5% normal swine serum to neurohypophysis (Fig. 2). These cells usually suppress nonspecific binding of immunoglobulins had an elliptic or spindly shape and occasionally to certain substances contained in the tissue. formed an elongated cellular process which had For the demonstration of PP-like immunoreac- a tendency to reach the capillary wall (Fig. 3). tivity, some sections, after an application of PP-positive cells were also scattered in the pars anti-BPP serum for 2 h at 4°C, were subjected to tuberalis (Fig. 9), especially near the infundibular indirect immunoperoxidase technique (24), using stalk. Almost none were seen in the pars distalis horseradish peroxidase conjugated anti-rabbit (Fig. 1). IgG-goat serum (1:40, Lot No. S 692, Miles On the other hand, numerous ACTI—I-im- Lab., U.S.A.). Other sections, after incubation munoreactive cells were observed in the pars with anti-porcine AC-TH serum for 12 h at 4°C, distalis, tuberalis, and intermedia. Their region- were stained with soluble horseradish peroxi- al distribution was similar to that of the PP- dase-rabbit anti-horseradish peroxidase (PAP) positive cells; the cells positive to the anti-ACTH complex (26), employing swine anti-serum to serum occupied the vast majority of the cell rabbit immunoglobulins (1:40, Lot No. 129B, population in the lower portion of the pars DAKO-immunoglobulins, Copenhagen, Den- intermedia (Fig. 5), but only a minority of the mark) and PAP complex (1:50, Lot No. 030, cell population in the upper portion of the pars DAKO-immunoglobulins). Finally, antigen- intermedia. As indicated by comparison of antibody binding sites were visualized with 3,3’- adjacent sections alternately stained for PP and diaminobenzidine-HZOZ mixture (4). the C-terminal of ACTH, the PP-immunoreactive cells were mostly the same as the ACTH-im- munoreactive cells. In the pars intermedia, a PP-LIKE SUBSTANCE IN PITUITARY 527 greater part of the endocrine cells indicated the 1;§jl1.j=_% .=.-.;= .. i I1.1.=1.j1:-=11;=€:-21:1-(é;?.i. 155- =I=f-1.=.i':=I :-I1.= :'.--I: -:-.-I;.:-__1;;.j_.;;5{Zigzag_=;{.1_-.;;;;;s;.;.r;.;-___ l _)<” J / / ii’-'i1':1:I3iI15.E_3.:;é-;.;:;:_::£:E_.;.é.5._-.;.:.__;-2-_i__.1._;__.-I.-::._5::.___.E._;;.1;;.'=_-,-_:;-_.-;:_-;;_1__-_:1;_:_;_ presence of both PP- and ACTH-like immunore- i ‘=£.= i<' >‘=‘>‘.'-'3i>;%§I;:'f'£r!§;£’1'3$ 1.97;,-1; ,-f§}$:?€:.'a1£;=.*./;;1 .-I-I:-;<'i.?3.>.?::'_i=1r='?£€!-L1;1j-I='r;1;-:-.'='-I:-.1-;.=-1:';==.1.= 1- .~ I’, .,-,.. , .g_.._._.?_.,_4,,;,,.;_{,;,;;,,\y=;,,..,_., ,3 ‘H activity (Figs. 4 and 5). However, ACTH-posi- K I » g 11 1-f:;-i;:_= '” I 53 ='11':'='I'= , / 4~’~'-’<'<'»'=1*fi=12113-*?~1§%<¥x~11:-1r/srfnaiiiiaw"-1>1¢::>;=a1;:*-z;-@;=:=9-,.-.,. ,.._.» ,- f>v->_ _,._.;_.,,.,_, . ....,_.._,>_.v_.,.., ._.._ _ _-51:: <1-.-.1 ';.=,<1<;ae€f.z?-7.’-};, .. .>1<;.r§<=-/.::§=-,.1§:,>;€,::‘;._.;:6-1',;> .1.’ ;;;e-‘-=-'.~ > >14;--,1=»,--;.':..-'.='<¢r>/://tie::sa4::;1éi¢b1§4~I=91.. =/-'.~-'>1is,1. .=£$~I<.-5.1;’:av/.2-'-Ir-<\'1:; 51:.-1.2!;11>;-=::.\1!<-=?ii?;=9'-.1-1:-=-=<-:><-:-1-,=.~1-:';='$55>1¢1»1.i.=1-== 1-=;-=1-'.4:.= .: /.:1-.;-1-=-1.; tive but PP-negative cells were often observed .1--;,=i=;;1;-,1,-;;,¢¢.r-23;-_-1;};->_>%*,:.<<,5"’-I‘¢=v'/'1-£'\'.'/.‘)4-:;='=-!i(i}I)))>7-""J;$4i>?'£§1%{I'>7E"$!I-Li5?>QL';:¢'¢\=}/.'v!.\|.;'{?'Q'-Q-1/,¢I‘I-6%’/df'IE{L§!\Y\';§,5{;)=_I§€'_;;-/.1==1. >;1e_».>;./-=<>.-,,4;- ;,-.~;\=1.,,;;.-g\11>_<.;;-;.-.5::-,>.';_.;:;:;.\§','.g=.:¢=;-:,1,1,=,-.;<<-, r~< __ :. L;13.‘-§-i'>'1--351;};?}1!E1.!1\;;“<:ir>1 2'/~‘§.{t>’!r1:/35%;-11 -’./{ii’t>i~1$>->'-=g-"2;§ <:£;?=‘.1'1~=<:-’>,\~=>-5-r15-mm=,-1-11;,-1.-1,':¢_.a ,.;':>1.r.1_-.1.==;;>;,1,-.;..-,-,-_-_=;,=;;---;:-.;_- and a small number of cells with no reactions for .v.~;_,=--: :1: ,/i.>2=_-’>;i=1,r,,;¢»:>;&>-}=,;;};;»>g1¢fé;{=~=_',;-" 541;.’/,:'_<;.;-;..=.,-'¢_<_.;11~> /__.!g'._:j<'$J>\5‘)"\'2<2§;?/{ff//,1‘-).5 ;, -1;-1/11,;-<-1_,<,<;4,-_:-éia‘3§;;;=;1-i;§:fi;;£-yfl»-:1gy.--.-.2-;.1-ti-:I;;-;-5::-I.;<2, .-.>;;..;.,<_-\.;,;;';1.,-_;*_¢,.;;;=;;,1»;;.3=_-.;..;;;;;=.;>;;;;;-I_',§,15'3=.>3;f.1_=1;-.1.;~j-_.-.'=1_1;->_;=.1_!.':1-1;1.-;.-;.>;:1;<-; i 11<.=.g_>f':;.3;.1.>,,=;:.&1‘;"€,»§¢Z i- , r ,.1.; ;-<.;-,-31>-2..-;i==,1:<i;§ —"_>':1f-;,/-.
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