Activity Of Pituitary Extracts Research Articles

The roles of FGFs in the early development of vertebrate limbs.

‘‘Fibroblast growth factor’’ (FGF) was first identified 25 years ago as a mitogenic activity in pituitary extracts (Armelin 1973; Gospodarowicz 1974). This modest observation subsequently led to the identification of a large family of proteins that affect cell proliferation, differentiation, survival, and motility (for review, see Basilico and Moscatelli 1992; Baird 1994). Recently, evidence has been accumulating that specific members of the FGF family function as key intercellular signaling molecules in embryogenesis (for review, see Goldfarb 1996). Indeed, it may be no exaggeration to say that, in conjunction with the members of a small number of other signaling molecule families [including WNT (Parr and McMahon 1994), Hedgehog (HH) (Hammerschmidt et al. 1997), and bone morphogenetic protein (BMP) (Hogan 1996)], FGFs are responsible for inducing and/or regulating the subsequent development of most organs in the vertebrate body. The purpose of this review is to discuss the functions performed by members of the FGF family in one of the best-studied vertebrate developmental systems—limb formation. It focuses initially on what is known about FGF function in the established limb bud and then discusses the mechanisms by which the signaling centers that control outgrowth and patterning of the established limb bud are formed, emphasizing possible roles played by FGFs in these processes. Finally, it discusses the potential role of FGFs in the induction of limb development. The insights into the requirement for FGF signaling in bone development that have been gained from analyses of mutations in human and mouse FGF receptor (FGFR) genes will not be discussed, as those studies have been the subject of several recent reviews (Wilkie et al. 1995; Yamaguchi and Rossant 1995; De Moerlooze and Dickson 1997; Webster and Donoghue 1997).

Pituitary-Specific and Hormonally Regulated Gene Expression Directed by the Rat Proopiomelanocortin Promoter in Transgenic Mice

All aspects of POMC biosynthesis exhibit tissue-specific regulation. The single copy gene is highly expressed in anterior lobe (AL) corticotrophs and intermediate lobe (IL) melanotrophs of the pituitary gland and in the arcuate nucleus of the hypothalamus. POMC gene transcription in corticotrophs is induced by hypothalamic CRH and vasopressin and inhibited by adrenal glucocorticoids, while in melanotrophs it is predominantly regulated by beta-adrenergic neural input and dopamine. To identify the rat POMC (rPOMC) gene sequences necessary and sufficient to target expression and hormonal regulation in corticotrophs and melanotrophs, we generated 13 transgenic mice carrying rPOMC fusion genes. The genes consisted of 706 or 480 basepairs of rPOMC 5' flanking sequences ligated to either the E. coli LacZ gene encoding beta-galactosidase or the K1 mutant of the SV40 large T-antigen gene. Overall, half of the transgenic lines had reporter gene expression in their AL and IL in a pattern indistinguishable from ACTH immunohistochemistry. In three of these lines, beta-galactosidase or K1 T-antigen was localized by double immunofluorescence exclusively to ACTH-positive corticotrophs and melanotrophs. Transcriptional regulation of the rPOMC-LacZ fusion gene in response to hormonal manipulation was quantified by a fluorescence assay for beta-galactosidase enzyme activity in pituitary extracts. There was a 15-fold increase in AL enzyme activity after adrenalectomy and a 3-fold increase in IL activity after haloperidol treatment. X-gal histochemistry of pituitaries from hormonally treated mice confirmed the cellular specificity of these effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in opiate activity of rat pituitary following acute administration of neuroleptics

An increase was found in the opiate activity of pituitary extracts obtained rom rats injected with the neuroleptic drugs trifluoperazine and sulpiride. The increase of opiate activity, measured by bioassay, was particularly evident 2 h after the administration of sulpiride. Dexamethasone completely prevented the neuroleptic-induced effect. Trifluoperazine and sulpiride may have affected dopaminergic mechanisms regulating endorphin storage in the pituitary.

An immunological study of a human pituitary interstitial cell-stimulating hormone.

SEVERAL investigators1–5 have reported recently the production of rabbit antiserum to human urinary gonadotrophins, but no similar data have appeared with respect to human pituitary gonad-stimulating substances. However, an immunochemical investigation in this Laboratory6 has shown that a highly purified preparation of sheep pituitary interstitial cell-stimulating hormone (ICSH) is a potent antigen. The rabbit antiserum obtained in that work6 was highly specific for the antigen and was able significantly to counteract its ability to stimulate the ventral prostate in hypophysectomized rats. By the Ouchterlony double diffusion test in agar-gel and the quantitative precipitin technique, the sheep interstitial cell-stimulating hormone was demonstrated to be homogeneous. Moreover, antiserum to sheep interstitial cell-stimulating hormone was capable of neutralizing significantly the interstitial cell-stimulating hormone activity of pituitary extracts from the rat, pig and whale, as well as of purified preparations of human pituitary interstitial cell-stimulating hormone and pregnant mare serum gonadotrophin. Injected anti-serum to sheep interstitial cell-stimulating hormone was also shown to cause an inhibition of endogenous activity of the hormone in normal rats. The results of similar investigations on the antigenicity of human pituitary interstitial cell-stimulating hormone are reported here.

Ophthalmotrophic activity in thyroidectomized guinea-pigs.

ABSTRACT The uptake of 35S-labelled sulphate by Harder's gland in guinea-pigs was studied under different endocrine conditions. It is concluded that a pituitary factor is able to stimulate the gland and that thyroxine somehow plays a role. This pituitary factor is neither the thyroid-stimulating factor nor growth hormone, but is present in thyrotrophic pituitary extracts. Most probably the sulphate uptake stimulating factor is identical with the ophthalmotrophic pituitary factor. The uptake of sulphate by Harder's gland has been used as an index of ophthalmotrophic activity in pituitary extracts as well as of endogenous ophthalmotrophic activity in thyroidectomized guinea-pigs. It is concluded that upon removal of the thyroid gland the pituitary response is rapid. A highly increased activity was shown within as little as 24 hours after thyroidectomy, which has been taken as a sign of increased secretion of ophthalmotrophin by the pituitary gland.

Inactivation of the adrenal ascorbic acid-depleting activity of pituitary extracts by ascorbic acid.

IF extracts of anterior pituitary are incubated for several hours in Ringer's solution containing 1–10 mgm./100 ml. ascorbic acid, their activity on the chromatophores of the isolated skin of Rana esculenta disappears1. Because of the close chemical relationship between adrenocorticotrophic hormone and intermedin, it seemed of interest to investigate whether the adrenal ascorbic acid – depleting activity of anterior pituitary extracts is also affected by ascorbic acid.

A quantitative method for measuring melanophore expanding activity.

ANUMBER of methods have been developed recently for the estimation of melanophore expanding activity in pituitary extracts. The majority of them are carried out in vitro utilizing isolated frog skin. There is, however, a need for a quantitative method of estimating melanophore expanding activity in vivo since there are indications that the melanophore responses in vivo are more specific for the melanophore expanding principle, and not influenced by many other substances that may be present in biological extracts (Sulman 1952a) (Schizume 1954). The available in vivo methods utilize the degree of melanin dispersion within the melanophores (melanophore index) estimated by microscopic observation as a measure of the response. It was felt that an objective measurement of the response should be used to obtain results that can be treated statistically and thus permit an evaluation of the accuracy and precision of the assay.

Influence of adrenotropic hormone fractions on adrenal repair and on adrenal ascorbic acid.

WE have studied1 the activity of pituitary extracts in the Sayers test2, which depends on ability to induce a rapid fall in the ascorbic acid content of the adrenal glands of hypophysectomized rats, and in an adrenal ‘repair’ test based on the increase in the adrenal weight of the rat hypophysectomized one to three weeks previously and given three intraperitoneal injections daily of pituitary extract for three days, the animal being killed on the fourth day. Since an adrenal weight-increasing effect (AW effect) does not necessarily measure only changes in the weight of active cortical tissue, such an effect is necessarily less precisely defined than an ascorbic acid reducing effect (AA effect). In our investigation of these two activities of different pituitary extracts, we have adopted as our standard for the ratio AW/AA the pig pituitary preparation 84–85 U, kindly supplied by Armour Laboratories, Ltd.; this preparation is about 2.5 times as active in the ascorbic acid reduction test as the Armour standard preparation La-1-A, the provisional International Standard. We have followed three main lines of investigation, which it will be convenient to consider separately.

Lipæmogenic Activity of Pituitary Extracts

Frazer and Stewart1,2 have described the chylomicron count method for assessing the level of blood-fat, and have used it to follow the effects of starvation and standard meals in man. Stewart3, using this method, has also observed lipaemias in rabbits after severe haemorrhage.

Golgi Apparatus as an Indicator of Secretory Activity in Pancreatic Islet Cells

Anselmino, Herold and Hoffmann1,2 claimed in 1933 to have demonstrated a “pancreotropic” activity of pituitary extracts. Their claims rested on experiments in which a crude extract of the pituitary body was injected into young rats; in a few days an increase in the number of the islets of Langerhans was observed. The increase in islet tissue was ascribed to the action of a substance normally present in the pituitary gland. These observations were confirmed by several authors3,4,5, and denied by others6,7,8. The majority of the investigators based their conclusions on anatomical and morphological variations of the pancreas islets, a somewhat subjective method of appreciating quantitative changes. The individual variations in the disposition and volume of the islets in the animals usually employed are unexpectedly large, and opinions based on inspection of microscopic sections, even serial sections, are unreliable. Richardson and Young9 have applied a quantitative method of estimating the ratio of islet-acinar tissue for Wistar rats, and have found that the mean value of this ratio in animals treated with a saline extract of fresh pituitary gland is double that of normal rats, a difference which is statistically significant. Extracts prepared by the methods used by Anselmino had no such effect.

Relation Between Amphibian Water Retention Principle and Oxytocic Activity of Pituitary Extracts

SummaryTwelve posterior pituitary extracts were found to contain 4 to 10 times as many amphibian water retention units per ml as international oxytocic units. Variation in the technics of assay prevented an estimation of the nicety of this correlation.