The temporal and spatial relationships between altered vascular function and cardiac muscle cell injury at the margins of developing myocardial infarcts were investigated, because such knowledge might provide potential for intervention in the evolution of myocardial infarcts and limitation of their size. Regional myocardial ischaemia was modelled in isolated rabbit hearts subjected to ligation of the ventral interventricular branch of the left coronary artery (0,30,60,120 or 240 minutes duration), the remainder of the heart being continuously perfused with oxygenated Krebs-Henseleit buffer solution. After the experimental ischaemic period, the whole heart was fixed by perfusion with phosphate-buffered 2.5% glutaraldehyde which, in preliminary studies, was shown not only to preserve the morphological appearance of cardiac muscle cells, but also to stabilise the distribution of flow through the myocardial blood vessels in the pattern pertaining immediately prior to fixation. Polymerising acrylic resin (L.R. White) was then injected into the vessels of the ischaemic and non-ischaemic regions simultaneously at identical pressures. Resin injected into the ischaemic region contained lead dioxide whilst that injected into the other vessels contained Fat Red 7B dye to allow identification of the source of supply of blood vessels within the heart. Cryofracture, freeze-drying and imaging by scanning electron microscopy (SEM) with a backscattered electron detector and low vacuum specimen chamber conditions were used. This made possible examination of transmural segments of myocardium spanning the margins of the ischaemic and control ventricular myocardium containing blood vessels filled by resin. SEM showed severe injury of cardiac muscle cells after 60 minutes of ischaemia, as characterised by separation and swelling of some organelles. Earlier ischaemic changes in some cells (focal increase in prominence of t-tubules and sarcoplasmic reticulum) were seen after 30 minutes. There was a transmural progression in development of irreversible injury from the subendocardium to the epicardium between 60 and 120 minutes corresponding to the "wavefront phenonenon". The lateral margins did not show such marked progression and were typically sharply demarcated on a cell-to-cell basis after 60 minutes. An increase in the proportion of functional capillary pathways (from 55% to 85%) in early (30 minutes) ischaemia was succeeded by a profound perfusion defect, corresponding to the "no-reflow" phenomenon, which had a very close temporal and spatial association with severe injury of cardiac muscle cells. Loss of patency was associated with increased proportions of collapsed, compressed capillaries and swollen myocardial cells. This study demonstrated that there is a significant region of myocardium which for a period shows intermediate degrees of myocyte injury (and is thus potentially salvageable) in the subepicardial portion of the developing infarct. Contrary to the claims of various authors similar potentially salvageable lateral "border zones" were neither large nor non-existent. Within 150 microns of the typically abrupt boundary, small discontinuous areas (<20% of this region) showed intermediate degrees of injury, and there was also an increased proportion of non-functional capillaries which were not collapsed or compressed, resulting in a 'low-flow' zone. This narrow lateral zone requires further investigation to determine whether it is static, and thus of negligible size, or whether it moves in advance of infarction and is thus pathogenetically significant.

Testicular function is stimulated from the pituitary gland by the gonadotrophic hormones FSH and LH. The testis in turn regulates gonadotrophin secretion by negative feedback. The agents of feedback are steroids, and in addition, probably a protein hormone, which has been given the name inhibin. A method capable of detecting inhibin-like activity in bull seminal plasma (bSP) was developed. Administration of bSP at the time of castration to five-week old male rats inhibited the post-castration rise of serum concentrations of FSH and LH otherwise seen 24 h later. The degree of inhibition depended on the dose; 0.5 ml bSP or the equivalent amount of bSP-extract always suppressed FSH and LH to levels typical of intact rats. The rats' sensitivity to 0.2 ml bSP varied with the time of year, possibly reflecting seasonal changes in the onset of puberty. The time-course of action of bSP-extract was studied in intact rats. Serum FSH was suppressed 12, 24 and 48 h after a single injection, but not at 3 or 6 h. LH was suppressed at 6, 12, 24 and possibly 48 h.

A procedure was developed to purify ovine placental lactogen (oPL) from fetal cotyledonary tissue of late gestation. A prolactin radioreceptor assay using mammary tissue membranes from the late pregnant rabbit was established and used to monitor lactogenic activity throughout the purification.

Chronic Fatigue Syndrome (CFS) is an illness characterized by persistent debilitating fatigue of uncertain origin. Precipitating and perpetuating factors of this illness are thought to be distinct and the aim of this thesis was to gain greater insight into the role of cognitive factors which may maintain the condition. This work was guided by two central frameworks, the self-regulatory model of illness representations and the cognitive taxonomy of psychopathology. These were used to define the different cognitive constructs and to investigate the way they function as a system to maintain pathological schema and disability in CFS. Three studies using different methodologies were conducted to test the hypotheses. The first employed a descriptive comparative design to ascertain whether CFS patients have unique cognitions which contribute to their disability over time. The sample was comprised of CFS patients without depression (n=39), CFS patients with a concurrent diagnosis of depression (n=14), patients with a primary diagnosis of depression (n=20); and healthy controls (n=38). The groups were matched in aggregate for age, gender, race, and education. Subjects completed the Cognitive Errors Questionnaire-Revised, which measures cognitive distortions relevant to both general and somatic events, and the Illness Perception Questionnaire, which measures the five dimensions of the illness representation in conjunction with other standard measures. Between-group analyses confirmed that the depressed group was distinguished by a low self-esteem, feelings of guilt and self-recriminations, the propensity to make cognitive distortions across all situations, and to attribute their illness to internal, stable and global factors. In contrast, the CFS patients were characterized by low ratings of their current health status, a strong illness identity, external attributions for their illness, and distortion in thinking that were specific to somatic experiences. CFS depressed patients had lower self-esteem than non-depressed patients and had the most pessimistic illness beliefs. A six month follow-up showed that CFS patients' cognitive structures and level of disability remained remarkably stable. Illness identity, serious consequences, somatic errors, and limiting coping accounted for a substantial proportion of the variance in CFS patients’ disability scores over time. These results are discussed in terms of their support for both of the cognitive models. CFS patients appeared to have distinct cognitions which were associated with ongoing disability. The subsequent two quasi-experimental studies were conducted in a single laboratory session. The first of these used standardized neuropsychological tests to determine whether psychological variables, particularly somatic focus, interfere with CFS patients’ performance on high load attention tasks. The discrepancy between CFS patients’ subjective reports of concentration and memory difficulties and objective evidence of these deficits was also investigated. The subjects included 25 CFS patients matched for age, gender, and intelligence with two groups of healthy controls. One of these groups underwent a somatic induction procedure as part of the investigation of the effects of somatic preoccupation on attention tasks. The tests included the verbal memory subscales from the Wechsler Memory Scale-Revised and the Paced Auditory Serial Addition Task (PASAT), a measure of divided attention and speed of information processing. The analyses of the induction data failed to support the validity of this procedure resulting in the somatic control group being dropped from the analysis. Consistent with previous studies the principal deficit in the CFS group appeared to be on the PASAT. The CFS group appeared to be less accurate than healthy controls in their appraisal of their performance, which were related to negative mood rather than objective performance. Depression was also related to high performance expectations in the CFS group, but not the controls. The results did not support the original assumption that somatic preoccupation contributes to neuropsychological difficulties in CFS. However, mood factors were clearly shown to impact on both the objective and subjective experience of symptoms. The aim of the final study was to investigate the concordance between the self-report data collected in study one and information processing biases in CFS. Comparisons of the CFS patients and healthy controls on a modified Stroop attention task and a self-schema memory task, found no evidence of an illness-related bias in CFS patients’ processing of information. Rather, they demonstrated a significant tendency to be distracted by and remember depressed-relevant stimuli. The exception was their propensity to make somatic interpretations. These results are discussed in terms of the defensiveness hypothesis, which proposes that CFS patients’ negative, external illness perceptions and somatic distortions may act as a defence against underlying feelings of low self-esteem. The complex nature of CFS patients’ cognitive structures was revealed and the need to use measures which do not rely on self-reports was clearly demonstrated. These studies provided further support for the central role of cognitive factors and mood in perpetuating CFS.

Several studies have shown that non-cycling cells are resistant to the cytotoxic effects induced by amsacrine (m-AMSA; 4'-(9-acridinylamino)methanesulphon-m-anisidide). This resistance may limit the activity of m-AMSA and related 9-anilinoacridine antitumour agents against solid tumours. The biochemical mechanism(s) for this resistance have been investigated using spontaneously transformed Chinese hamster fibroblast (AA8 cells) in log- and plateau-phase spinner cultures. In early plateau phase most cells entered a growth-arrested state with a G1-G0 DNA content and showed a marked decrease in sensitivity to cytotoxicity after a 1-h exposure to m-AMSA or its solid tumour-active analogue, CI-921. Studies with radiolabelled m-AMSA demonstrated that changes in sensitivity to m-AMSA-induced cell killing were not due to a difference in uptake or retention of drug by log- and plateau-phase cells, and there was no significant metabolism of drug by either log- or plateau-phase cells. Thus, after a 1-h exposure to [3H]-m-AMSA at 37°C, a small proportion (1%) of cell-associated radioactivity was covalently bound to macromolecules, but most of the cell-associated radioactivity represented unchanged m-AMSA. There was no evidence for any oxidative metabolism to reactive quinoidal species in these tumour cells. However, studies with a fluorescence assay for DNA unwinding indicated that plateau-phase cells were 3 to 4 times less sensitive to m-AMSA-induced DNA breakage than log-phase cells, and changes in sensitivity to m-AMSA-induced DNA breakage correlated with changes in sensitivity to cell killing by m-AMSA as cell progressed from log to plateau phase. Further studies showed that the decrease in sensitivity to m-AMSA-induced DNA stand breakage correlated with a decrease in sensitivity to covalent DNA-protein complex formation in plateau-phase cells after m-AMSA treatment. Combined with evidence that the DNA lesions rapidly disappeared from both log- and plateau-phase cells following the removal of m-AMSA (half-time approx. 4 min), this indicated that the lesions detected by the FADU assay probably arose from the stimulation of DNA-topoisomerase II (topo II) cleavable complex formation by m-AMSA. K+/SDS precipitation assays with [32p] 3’-end-labelled pBR322 DNA indicated that nuclear extracts containing topo II activity from plateau-phase cells were 3- to 4-fold less sensitive to stimulation of DNA-topo II complex formation by m-AMSA than nuclear extracts from log-phase cells. This change in sensitivity to m-AMSA-induced DNA-topo II complex formation was therefore similar to that observed with intact cells. However, P4 unknotting assays indicated that topo II activity in nuclear extracts from plateau-phase cells was only 2-fold lower than that in nuclear extracts from log-phase cells. Resistance to treatment with m-AMSA may therefore reflect a decrease in topo II activity and/or a decrease in sensitivity of topo II enzymes to stimulation of cleavable complex formation by m-AMSA in non-cycling cells.

Members of the integrin superfamily of adhesion molecules are involved in cell to cell, cell to ECM, and cell to pathogen interactions, and are of fundamental importance in many biological processes. The β7 integrins α4β7 and αEβ7 have evolved to play specialized roles in gut mucosal immunity. α4β7 mediates the homing of lymphocytes to intestinal Peyer's patches, mesenteric lymph nodes, and the lamina propria by binding to the vascular addressin MAdCAM-1 (Fong et al., 1997). αEβ7 binds epithelial E-cadherin retaining lymphocytes at the intraepithelial compartment of the mucosa. The expression of αEβ7 is induced on migratory lymphocytes by TGF-β secreted by gut enterocytes. The signalling mechanisms responsible for basal and TGF-β-induced expression of β7 integrins are not well understood. Previous studies identified two TGF-β1 response regions in the β7 gene promoter termed TGFBRR-1 and TGFBRR-2 encompassing nucleotides -509 to -398 and -121 to -34. Here, TGF-β1 activation of the β7 gene proximal promoter is shown to be mediated by MAPK family members. TGF-β1 stimulation of TK-1 T cells increased the steady-state mRNA levels of the β7 gene relative to α4 transcripts, and led to enhanced phosphorylation of c-Jun. TGF-β1 stimulation induced rapid increases in the binding of nuclear protein complexes to TGFBRR-1 and -2. Sp1 and Sp3 which mediate TGF-β1 signalling were shown to bind to an Sp1 cis-element encompassing nucleotide positions -67 to -60 within TGFBRR-2. The interaction of Sp1 with its cognate binding site was c-Jun dependent. In contrast, there was no evidence for involvement of the Smad proteins. ATF-2 was identified to bind to a region encompassing nucleotide positions -699 to -689 just upstream of TGFBRR-1. Sp1 and ATF-2 expression vectors co-transfected into Sp1-deficient SL-2 cells synergized to drive the activity of a β7 gene luciferase reporter. Mutation of the ATF-2-binding site modestly reduced β7 gene reporter activity. The involvement of c-Jun in TGF-β signalling and interaction of Sp1 with the β7 gene promoter suggested that MAP kinase pathways might mediate β7 gene transcription. Specific chemical inhibitors were used to ascertain which of the three MAPK pathways namely p38, JNK, and ERK were involved. Results obtained by nuclear run-on transcription analysis which measures nascent RNA synthesis showed that both the p38 and JNK pathways regulate β7 gene expression in TK-1 cells, whereas only the p38 pathway regulates α4 gene expression. Thus, treatment of TK-1 cells with the p38 inhibitor SB203580 and the JNK inhibitor SP600125 inhibited the synthesis of β7 transcripts, whereas only SB203580 inhibited the synthesis of α4 transcripts. Conversely, sodium arsenite which induces JNK and p38 upregulated nascent synthesis of α4 and β7 RNA transcripts. SB203580 blocked the binding of nuclear factors to TGFBRR-1, and ATF-2 binding to nucleotide position -699 to -689. Similarly, SP600125 blocked the binding of Sp1 and Sp3 to TGFBRR-2, whereas unexpectedly SB203580 enhanced their binding. Furthermore, both SB203580 and SP600125 decreased cell-surface expression of the β7 subunit and SB203580 inhibited TK-1 cell adhesion to MAdCAM-1. In contrast, the MEK inhibitor PD98059 had no effect on the expression of nascent β7 RNA transcripts and cell-surface expression of the β7 subunit, suggesting that the ERK pathway is not involved in regulation of β7 gene expression in TK-1 cells. In contrast to the results obtained with TK-1 cells, SB203580, SP600125, and PD98059 each inhibited the nascent synthesis of α4, β7, and αE transcripts in peripheral blood lymphocytes. In conclusion, this study has revealed for the first time that both the p38 and JNK pathways mediate TGF-β1-induced expression of the integrin β7 gene. Expression of the β7 gene is Sp1-dependent, and involves the synergistic cooperation of c-Jun and ATF-2. It is proposed that the p38 and JNK pathways play a role by triggering the activation and translocation of c-Jun and ATF-2 to the nucleus. / Whole document restricted, but available by request, use the feedback form to request access.

Lactose malabsorption (LM) in children was diagnosed by an elevated breath hydrogen (BH) level following a 10g lactose load. A portable gas chromatograph and a semiconductor detector, designed and constructed for use in the Pacific Islands is described. Following verification on known malabsorber and. normal subjects, the technique was used to determine the prevalence of LM in Europeans at Auckland and Rarotonga, and in Samoans at two locations in Auckland and two locations in Western Samoa. The prevalence of LM in Europeans was significantly (p<0.01) higher at Rarotonga than at Auckland. For Samoans, the prevalence of LM was significantly (p<0.01) higher in Western Samoa than at Auckland. The prevalence of LM was very highly significantly (p<0.001) related to race. Each child tested for LM filled in a questionaire to determine attitude, consumption of and perceived intolerance to milk, milk biscuits and ice cream. Lactose malabsorption was significantly (p<0.05) correlated to milk consumption and to attitude to dairy products, but not to sex, age, and perceived intolerance. The consumption of dairy products was very highly significantly (p<0.0001) correlated to attitude, and highly significantly (p<0.001) correlated to location and perceived intolerance. There was no significant correlation between consumption and race, sex or age. Perceived intolerance to individual dairy products was significantly correlated to attitude to milk (p<0.0001), milk biscuits (p<0.02) and ice cream (p<0.001). Perceived intolerance was not related to age, sex, race, location or the actual symptoms following the consumption of 10g lactose. The unexpected finding of increased LM in the Pacific Islands, was investigated further by studying the LM status of the Medical Team during a visit to western Samoa, and by performing a microbiological survey of water quality. It was found that half of the Medical Team 3/6, became malabsorbers during the week spent in Western Samoa. On returning to New Zealand it was shown that lactase levels took 3 months to normalise. The water supply in Western Samoa was shown to contain very high levels of coliform bacteria. The currently held hypothesis that genetic factors are solely involved in the onset of LM, was not supported. The evidence from the survey supported environmental factors are also involved in adult onset LM. The hypothesis suggesting that dietary lactose was a requirement for retaining elevated lactase levels, was tested using Galactosemic and Phenyl Ketonuria patients. None of the patients had developed LM although they had been on a low lactose diet for years, hence the theory was not supported. The BH method proved highly successful in diagnosing LM with many of the children actually enjoying it.

In newborn infants, birth asphyxia represents the predominant cause of brain injury. These infants will later exhibit neurodevelopmental disabilities or a more major cerebral palsy. Prevention of adverse outcomes requires an understanding of the way in which these deficits develop. Endogenous protective mechanisms arising from the insult have opened new insights in neuroprotective strategies. Neurotrophic factors such as IGF-1 and its N-terminal tripeptide GPE have been shown to confer some neuroprotection after HI injury in the adult rodent. In the P21 rat brain after moderate HI injury, exogenous intracerebral and intraperitoneal injections of GPE (30μg and 300μg respectively) were neuroprotective in the hippocampus and lateral cortex possibly through binding to glia as detected by autoradiography of 3H-GPE. In the preterm infant the mechanisms of white matter injury remain to be clearly elucidated. To mimic the pattern of diffuse cerebral injury of the very preterm infant, a transient moderate focal HI injury has been applied on the immature P3 rat. This new model showed a significant reduction in the lateral cortical volume with reduction and alteration of the myelination pattern in the cortical white matter (WM) at P21. These cortical alterations result from neuro-axonal damage 24h after the insult as shown with Fluoro-Jade B staining and β-APP accumulation. In addition activated astrocytes from 24h after HI up to P21 were present. This model should enable us to elucidate some of the pathogenic mechanisms involved in diffuse WM injury. Brain damage in the developing brain has two components: 1) the pattern and mechanisms of injury are correlated with the stage of development at the time of injury; 2) it will influence subsequent brain development.

Ischaemic cell death has been implicated in a number of retinal diseases, including glaucomatous neuropathy, proliferative diabetic retinopathy and a range of vascular diseases. The cascade of events leading to cell death involves both cellular metabolic changes and a functional component. However, it is yet unknown how long these changes persist, whether all cell classes are affected, and the characteristics of recovery. Moreover, there have been few studies correlating the neurochemical changes with the ensuing functional changes. The aim of this thesis was to track the metabolic and functional recovery of the ischaemic rat retina, given the premise that: (1) amino acid neurochemistry reflects metabolic integrity and cellular identity, and; (2) the permeation of a cation channel probe called agmatine reflects channel functionality. Quantitative pattern recognition analysis of overlapping amino acid and agmatine expression profiles were used to provide a statistically robust classification of cells according to metabolic and functional characteristics. This classification was spatially complete and with single cell resolution. Finally, the electroretinogram was used to also assess retinal function and corroborate the observed neurochemical changes. These measures were taken at intervals for up to two weeks of reperfusion. The results show that by 48 hours of reperfusion, amino acid metabolism had returned to near normal levels, although cell classes were missing, and there was persistant cation channel gating anomalies. Immunocytochemical labeling identified a preferential loss of cone bipolar cells, with all remaining rod bipolar cells showing increased cation channel gating. The electroretinogram and agmatine experiments showed that this dysfunction is likely due to abnormal glutamate release from pre-synaptic photoreceptors, detected by changes in post-synaptic agmatine permeation, and not due to the presence of anomalous metabotropic glutamate receptors. Cholinergic amacrine cells demonstrated persistant neurochemical labeling, but did not show cationic flux following stimulation by glutamate agonists. In conclusion, the retina shows remarkable recovery in the amino acid metabolism, although functional changes persist. Finally, structural integrity or immunocytochemical labeling does not necessarily imply that cells maintain functional receptors, or that neurotransmitter release is normal secondary to disease. / Whole document restricted, but available by request, use the feedback form to request access.

Ovine placental lactogen (oPL) is secreted by the placenta into both the fetal and maternal compartments. Its biological function(s) during pregnancy and the mechanisms involved are still unclear. A purification procedure was developed for oPL from sheep placental cotyledons of late gestation. Four procedures were attempted to obtain homogeneous oPL. Recoveries of oPL and total protein were measured throughout the several procedures using a specific oPL RIA and the Bradford protein estimation respectively. The third and fourth procedures resulted in homogeneous oPL and a partial amino acid sequence was obtained from the fourth procedure. In the successful procedures, the placental tissue was extracted with 0.1 M ammonium bicarbonate pH 8.5. A pH precipitation of the soluble fraction was performed, followed by 60% saturation with ammonium sulphate. Further separation steps involved chromatogaphic procedures. Carboxymethylcellulose (CM32) cation exchange was performed batchwise at pH 5.6. Subsequently chromatofocusing was performed to elute proteins in order of their isoelectric points. This was carried out using a pH gadient of 0.9 to 6.0. The final chromatographic step was reverse-phase high performance liquid chromatography (RP-HPLC) using a C4 column. To obtain homogeneous oPL in the third procedure, the partially purified oPL was subjected to SDS polyacrylamide gel electrophoresis and the separated proteins were transferred to nitrocellulose membrane. The homogeneous oPL was eluted from the membrane, however, sequencing was unsuccessful. It was assumed that the N terminal of oPL was blocked. Homogeneous oPL was obtained in the fourth procedure by electrophoretic elution from the Hunkapiller gel system performed at 4°C. The oPL was digested with trypsin, the fragments were separated by RP-HPLC chromatography and two peptides were sequenced. Peptide 1: F D E Q Y G Q G I Peptide 2: Y I N C H T Several strategies were attempted to provide more homogeneous oPL to enable more sequencing. The partially purified oPL fractions from each of these attempts were pooled and electrophoresed on an SDS polyacrylamide gel. The section of acrylamide containing the oPL band was homogenised and a trypsin digest was performed. The digested oPL was separated from the gel pieces, filtered through a Sep-Pak filter and the fragments were separated by RP-HPLC. The yield of oPL was low, but sufficient homogeneous oPL was obtained to provide a partial amino acid sequence from tryptic peptides. A further two peptides provided sequences. Peptide 3: (L) A G E M V N R F D E Q Y G Q G I Peptide 4: (L) Q P G K C Q I P L Q S L F Collaborators from Genentech Inc (San Francisco USA) used partially purified oPL produced from the present study and also obtained homogeneous oPL (Colosi et al., 1989). Complementary DNA clones of oPL were isolated and expressed in mammalian cells by recombinant DNA techniques (Colosi et al., 1989). These clones were sequenced, demonstrating that the full sequence of oPL consists of 198 amino acids preceded by a 38 amino acid sequence signal. Recombinant oPL was generated by Colosi et al. (1989) which provided sufficient material to perform physiological studies in vivo. The somatogenic effects of recombinant oPL were investigated in the growth hormone (GH) deficient dwarf rat and compared to identical doses of recombinant bovine GH (bGH) in 3 independent studies. Both oPL and bGH treatments resulted in an increase (p<0.05) in body weight gain compared to that in saline treated controls, with oPL treatment being more potent than bGH (p<0.05). In promoting linear growth, oPL was more potent (p<0.05) than bGH in some instances. Nitrogen content of dry carcass matter was increased with oPL treatment compared to saline (p<0.05), with a nonsignificant increase in bGH treated animals. Carcass fat was similarly reduced by both oPL and bGH treatment (p<0.05) compared to saline. Serum insulin-like growth factor I (IGF-I) concentrations were increased significantly (p<0.05) by both oPL and bGH treatments, with a significantly greater effect of oPL suggested in one study. No increase in hepatic IGF-I mRNA was evident with either treatment, suggesting that the increase in serum IGF-I is due to posttranscriptional mechanisms. The expression of IGF binding protein 3 (IGFBP-3) hepatic mRNA was increased (p<0.05) with bGH treatment compared to that after saline treatment, but was unaffected by opL treatment, indicating regulation by GH at the transcriptional level. The binding of [125I]bGH to hepatic membrane preparations demonstrated no difference in specific binding compared to that in saline controls. However, [125I]oPL specific binding was greater in oPL treated animals (p<0.05). Animals treated with bGH had reduced (p<0.05) hepatic GH receptor mRNA compared to saline controls, but oPL treatment had no effect. Thus, oPL is a potent anabolic and lipolytic agent in the dwarf rat, exerting greater somatogenic effects on some parameters than bGH. The studies in this thesis have described biochemical and biological characterisitics of oPL. The amino acid sequence of oPL is more closely related to prolactin (PRL) than to GH (Colosi et al., 1989). However, oPL has potent somatogenic activities in the GH deficient dwarf rat. Our data suggest differences in receptor binding and effects on GH receptor and IGFBP-3 expression with these two treatments, raising the possibility of actions through different pathways or differential effects at the GH receptor level. These results do not fully resolve whether GH and PRL exert all effects through a single receptor or whether there is a separate PL receptor.