Sharon M. Russell

Effect of mammalian thyrotropin releasing hormone on prolactin secretion by bullfrog adenohypophyses in vitro

The effects of the mammalian thyrotropin-releasing hormone (TRH) on the secretion of prolactin by bullfrog adenohypophysis in vitro were investigated in short-term incubation and 24-hr organ culture experiments. Prolactin in the medium or in the incubated tissue was measured by either polyacrylamide disc gel electrophoresis and densitometry or by a homologous radioimmunoassay. The TRH was consistently effective in promoting prolactin release in vitro in concentrations of 10 ng/ml to 10 μg/ml. The tripeptide also caused an increase in the tissue prolactin content over a wide range of concentrations. These results indicate that TRH may function as a prolactin-releasing factor in the bullfrog.

Growth and Differentiation of Fetal Rat Intestine Transplants: Dependence on Insulin and Growth Hormone

We have studied the role of hormones in the growth and differentiation of fetal rat intestine. Pieces of small intestine from 15-day fetal rats were transplanted under the renal capsule of either normal, hypophysectomized (HX), or diabetic adult rats and grown for 11 days. Intestine transplants in control hosts showed normal differentiation and they increased 60-fold in protein content and wet weight. Growth of transplants in HX and diabetic hosts was reduced by 50 and 25%, respectively. Transplants in diabetic hosts were histologically normal, while those in HX hosts failed to develop villi and discrete smooth muscle layers. Normal growth and differentiation in HX and diabetic hosts were completely restored by administration of growth hormone (GH) or insulin, respectively. Our data indicate that both GH and insulin are necessary for normal growth of the transplanted intestine during a period corresponding to late fetal and early neonatal life, but only the former is required for normal differentiation.

Comparison of secreted and extracted forms of rat pituitary prolactin

Prolactin secreted by rat anterior pituitary explants into organ culture medium was purified by salt fractionation and gel filtration. A yield of 22 mg/g was obtained, which clearly represented de novo synthesis and secretion of the hormone. Comparative characterization studies were performed on the secreted prolactin and pituitary extracted rat prolactin obtained from the National Institute of Arthritis, Metabolism and Digestive Disease. The biological and immunological activity estimates of both forms were comparable, although the specific activities of the secreted prolactin were somewhat lower than those of the pituitary prolactin. The secreted and extracted forms of prolactin appeared to be identical in primary structure as evidenced by similar amino acid compositions and identical NH2-terminal sequences. Circular dichroism spectra suggested that there may be differences in tertiary structure, since the positive tryptophan band at 292 nm, which eas observed with extracted hormone, was absent in the secreted prolactin.

Electrophoretic separation of forms of rat growth hormone with different bioassay and radioimmunoassay activities: comparison of intraglandular and secreted forms

Abstract Rat adenohypophysial tissue and medium in which pituitary explants had been incubated were processed by polyacrylamide disc gel electrophoresis (pH 9.5). Eluates of 6 regions of the gel columns were tested for growth hormone (GH) by a bioassay (BA; rat tibia test) and a radioimmunoassay (RIA). In the tissue, both assays detected most of the GH (80–99%) in segments with an R f range of 0.30–0.56. In the medium, both assays recorded a more cathodal distribution of most of the hormone (85–96%) in the R f region 0.00–0.42. The BA/RIA ratios of the segment containing the prominent stainable GH band (R f range 0.30–0.42) varied from 0.6–1.8 in tissue and medium. The tissue contained slow migrating (R f range 0–0.29) GH that had a high BA/RIA ratio (11.1–25.7). The medium contained high ratio GH (32.7–33.8) in a more anodal location (R f 0.57–0.68). Purified rat prolactin (RP-I) was not active in either the BA or the RIA. The results indicate that rat GH exists in electrophoretically heterogeneous forms which differ in their BA/RIA activity ratios. The proportion of these forms stored in adenohypophysial tissue and secreted by the gland may differ.

An Insulinlike Growth Factor I-Resistant State in Cartilage of Diabetic Rats Is Ameliorated by Hypophysectomy: Possible Role of Metabolism

This study investigated the effect of IDDM on cartilage anabolic activity in rats. Rats were injected with STZ to induce IDDM, were hypophysectomized, or were injected with STZ and hypophysectomized. After 14 days, control (intact and sham-Hx) and Hx rats were normoglycemic, whereas the rats with IDDM exhibited hyperglycemia and glycosuria. The HxDb rats, however, had normal blood glucose levels and no glycosuria. Both growth, serum levels of IGF-I, and basal cartilage 35SO4 incorporation measured in vitro were decreased in the Hx, IDDM, and HxDb groups. IGF-I added in vitro significantly stimulated 35SO4 incorporation by cartilage explants from control and Hx animals, whereas explants from the animals with IDDM were unresponsive. Explants from the HxDb rats, however, were stimulated by IGF-I in a dose-related manner. Because Hx corrected the glycemic status of the IDDM rats and restored cartilage responsiveness to IGF-I, a second set of experiments was undertaken to further investigate the relationship between cellular metabolism and anabolic activity in cartilage. Cartilage explants from rats fasted for 48 h showed significantly decreased basal 35SO4 incorporation, which was as low as that in explants from rats with severe IDDM. Whereas explants from the IDDM rats were completely unresponsive, those from the fasted rats (and fed rats) were significantly stimulated by the added IGF-I. However, incubation in the presence of 2-D-G, which causes intracellular glucopenia, or in the absence of glucose, completely blocked the anabolic response to IGF-I in otherwise responsive tissues. In conclusion, an important component of diabetic growth inhibition appears to be tissue resistance to the anabolic action of IGF-I, a condition that is correctable by Hx and that may be a result of metabolic impairment at the tissue level.

Mozart, Alexander the Great, and the animal rights/liberation philosophy.

FEW SCIENTISTS, MUSICIANS, MILITARISTS, or historians would readily discern parallels between the death of Wolfgang Amadeus Mozart in 1791 and that of Alexander the Great 2114 years earlier, and yet there are several. Both historically prominent figures suffered untimely deaths in their midthirties and both succumbed to diseases that most likely could have been prevented, cured, or at least treated if they had lived today (1, 2). More significant is the fact that the art and science of medicine when Mozart died were scarcely more advanced than they were at the time of Alexander’s demise. Thus, remedies available to treat the sick when Mozart and Alexander died were almost equally limited in their availability and efficacy. This conclusion is supported by the data in Fig. 1, which show that about 80% of our present biomedical knowledge has accrued since 1800 and more than 50% was acquired during the present century. The rapid rise in medical knowledge after 1800 can be attributed in large part to the increased use of animals in research. Physicians recognized that there was little hope of coping with human illness until they first understood how living systems function when they are healthy. During the first quarter of the 19th century, animal studies were crucial for fewer than one-third of the major advances that occurred (Fig. 2). Thereafter, however, research with animals contributed to more than half of the significant discoveries; during some periods animal studies accounted for more than 75% of the major advances. Overall, between 1901 and 1975, animal research contributed in a significant way to 74% of the 386 major biomedical advances listed by Hellemens and Bunch (3). This proportion is in excellent agreement with an independent estimate of the extent to which research with animals has contributed to important advances in biomedical knowledge. Seventy-one percent of the 82 Nobel prizes for Physiology or Medicine awarded between 1901 and 1982 were given for research that depended on studies with animals (4).

Growth and differentiation of transplanted rat embryos in intact, diabetic and hypophysectomized hosts: comparison with their growth in situ.

The objectives of this investigation were to evaluate the suitability of a transplant system for studying the endocrine control of growth and differentiation in rat embryonic/fetal tissues, and to gain information on the development of their hormone dependence. Whole 10-day-old rat embryos were transplanted under the kidney capsule of intact, hypophysectomized (Hx) or diabetic (Db) juvenile syngeneic female hosts, and grown there for 3, 6, 9 or 12 days. The wet weight, DNA and protein content of the transplants and of age-matched in situ embryos/fetuses were measured to assess their growth. The transplants in intact hosts increased more than 300-fold in all parameters during 12 days of incubation. However, this increase was only about 4% of the in situ growth. The severe impairment in growth occurred mainly during the first 3-day period when the transplants grew only 5% as much as the in situ embryos. Between days 13 and 22 of gestational age, the increment in transplant growth was 70% of that occurring in situ. Tissue differentiation of the transplants in intact hosts was essentially normal, although they grew as teratomas. Growth and differentiation of transplants in Db and Hx hosts were delayed or inhibited. This inhibition occurred as early as day 3 after transplantation and was corrected by appropriate hormone replacement therapy of the hosts. We conclude that rat embryos/fetuses develop a dependence on a growth hormone-dependent factor (possibly somatomedin) and/or insulin for growth before day 13 of development. This transplant system will be useful for studying other aspects of the control of growth and differentiation of rat embryos/fetuses between days 10 and 22 of gestation.

REPLY TO SINGER'S BLIND HOSTILITY

We were not surprised by the tone of Peter Singers response to our commentary but we admit to astonishment at the minor points of criticism that he selected to attempt to rebut. To paraphrase part of his reply to our first, abbreviated critique (1) of his chapter (2), we conclude that his failure to respond to our disclosure of his numerous distortions and selective quotations, or to our discussion of the flimsy basis for his philosophical arguments, or to our conclusion that his position reflects misanthropic and anti-science sentiments, constitutes his reluctant endorsement of the validity of these points in our critique. The Non-Issue We readily admit that we were in error in originally suggesting that Singer had fabricated a quotation. We are puzzled, however, that Singer is making such an issue of an error that we corrected before publication. The reason that Singer received a second revised manuscript for his comments in January of 1995 was that the manuscript was critiqued by two outside reviewers, the four members of the Publication Committee, and the Editor-in-Chief, many of whom made individual comments and suggestions for minor revisions, primarily in the tone of certain wording. This process took several months. We readily agreed to the proposed changes because none of them was substantive, and none pertained to any of the material Singer brought up for discussion in his original response. (We had deleted a reference to our erroneous allegation which was inadvertently left in our first revision, and to which Singer objected, before we even received his initial commentary.) When some 8 months passed without a reply from Singer, we assumed that he was using the time to prepare a more thorough rebuttal to our major criticisms. To our surprise, his response when finally received was almost identical to his first one.

Differential Effects of Somatostatin on the Release of Bioactive and Immunoactive Rat Growth Hormone in vitro

The effects of linear (L) or cyclic (C) somatostatin (SRIF) on the release of growth hormone (GH) as measured both by bioassay and by radioimmunoassay (RIA) were studied in a series of incubation experiments with rat adenohypophyses. Although both forms of SRIF inhibited release of RIA-GH in all experiments, only C-SRIF appeared to inhibit release of bioactive GH. L-SRIF even enhanced release of bioassayable GH in one study. Addition of C-SRIF to medium containing secreted GH strongly inhibited the tibial growth response of the bioassay animals, while it had no effect on the measurement of GH by the RIA. Thus, the apparent inhibitory effect of C-SRIF on release of bioactive GH may be an artifact. The conclusion was supported by experiments in which the SRIF was not removed from the medium prior to assay by dialysis or by neutralization with anti-SRIF antiserum. After these manipulations, the inhibition by C-SRIF of the secretion of bioactive GH was eliminated, whereas the inhibitory effect on RIA-GH release was not affected. These results support other evidence for the differential release of rat GH with varying immuno-and bioactivities by different stimuli.

The unnatural nature of the animal rights/liberation philosophy.

The contemporary animal liberation or animal rights movement (ALARM; we have modified the acronym used by Vance [2]) is derived from antivivisectionist organizations that emerged in Europe and North America during the 1800s (3). The term animal rights is more commonly used in the United States, whereas the label animal liberation is preferred in Europe and elsewhere. In the United States, the ALARM has taken over many well-established animal welfare organizations and has diverted their functions and resources away from welfare and toward opposition to all animal use by humans. By this means, the ALARM is now masquerading behind a facade of animal “protectionism” and is making inroads into the environmental movement as well (4). Members and supporters of animal “protection” organizations are not all of the same mold. They have been classified into three groups by Jasper and Nelkin (5): welfarists, pragmatists, and absolutists. The welfarists are concerned about animal well-being and are not keenly supportive of animal “rights.” The pragmatists believe that animals should have rights, but they recognize that some use of animals by humans will be necessary for the foreseeable future. The absolutists, who have also been called fundamentalists by Galvin and Herzog Jr. (6), are the extremists of the movement, who insist that all human use of animals must stop immediately. Most of the pragmatists are probably omnivores but the absolutists are likely to be strict vegetarians or vegans. They consume no animal products whatsoever—no dairy products, eggs, or even honey—and they eschew all use of animals for clothing, even silk, since its production involves killing worms. These fundamentalists, and some of the pragmatists, believe that all animals have rights equal to those of humans (or that they deserve at least equal consideration) and should therefore not be exploited by humans.