PubMed Health⌕ Search

Biomedical subjects

P A Sinclair

Publications and source records attributed to P A Sinclair.

11 recordsLinked to original sources
PubMed2006

Molecular cloning and regulation of porcine SULT2A1: relationship between SULT2A1 expression and sulfoconjugation of androstenone.

Hydroxysteroid sulfotransferase (SULT2A1) is a key enzyme in the testicular and hepatic metabolism of 5alpha-androstenone, which is a major component of the off-odor and off-flavor in pork known as boar taint. The goals of this study were to determine the role of testicular and hepatic SULT2A1 activity on plasma 5alpha-androstenone sulfate levels, the accumulation of 5alpha-androstenone in adipose tissue, and to gain insight into the regulatory control of SULT2A1. Testicular SULT2A1 activity was negatively correlated (r = -0.57; P < 0.01) with 5alpha-androstenone concentrations in fat. The differences observed in SULT2A1 activity warranted investigation into potential genetic variation within porcine SULT2A1. The cDNA sequence of porcine Sult2A1 was determined to be > 82% homologous to the human, mouse, and rat Sult2A1 genes. A single nucleotide polymorphism was detected within the coding region of the Sult2A1 from individual testes and liver samples; however, this did not affect the amino acid sequence of the enzyme. Western blot analysis determined that animals with high concentrations of 5alpha-androstenone in fat and low SULT2A1 activity had corresponding low levels of SULT2A1 protein compared with animals with low levels of 5alpha-androstenone in fat. Real-time PCR analysis indicated that Sult2A1 mRNA was increased 2.8-fold in animals with high levels of the protein relative to animals with low levels of the protein. Furthermore, we demonstrated the positive role of the nuclear receptors constitutive androstane receptor and pregnane X receptor, as well as the possible role of farnesoid X receptor in the regulation of testicular SULT2A1 activity. Together, the results of this study suggest that differences in SULT2A1 expression can influence 5alpha-androstenone accumulation in fat.

Adipose Tissue↗
PubMed2006

The boar testis: the most versatile steroid producing organ known.

A review of the remarkable production of steroids by the testes of the boar is presented, with the principal aims of highlighting the achievements of the Leydig cells and, at the same time, pointing to the considerable deficiencies in our understanding of its biological relevance. The onset of gonadal steroidogenesis at an early stage of sex differentiation and the pattern of pre- and postnatal secretion of steroids are outlined. This is followed by a list of steroids identified in extracts of the boar testis, with emphasis on those that can reasonably be assumed to be secretory products of the Leydig cells. For example, the high concentrations of 16-unsaturated C19 and sulphoconjugated compounds are noted. Next, an impressive list of steroids found in venous blood from the boar testis is given; among them are the 16-unsaturated steroids, the oestrogens and dehydroepiandrosterone, all mainly in the form of sulphates. However, the list also includes some less likely members, such as 11-OH and 19-OH androgens as well as 5alpha-reduced steroids. Lastly, the high concentrations of steroids reported in testicular lymph, especially sulphates, are mentioned. Although roles for testosterone are uncontested, and even for the pheromone-like C19 steroids, there is little that can be said with assurance about the other compounds listed. Some speculations are made on their possible contributions to the reproductive physiology of the boar. This is done to provoke interest and, perhaps, even action towards reaching a more complete understanding of the biological significance of the steroidogenic powers of porcine Leydig cells.

Animals↗
PubMed2005

Metabolism of the 16-androstene steroids in primary cultured porcine hepatocytes.

The hepatic metabolism of the 16-androstene steroids was investigated using isolated porcine hepatocytes. This study demonstrated that the liver is capable of producing both phase I and phase II steroid metabolites from 16-androstene steroid precursors. 16-Androstene metabolites were recovered by solid-phase extraction and identified by gas chromatography-mass spectrometry (GC-MS). When 5alpha-androstenone was provided as a substrate, both 3beta- and 3alpha-androstenol were produced as well as a metabolite that showed evidence of hydroxylation. Incubations with the various 16-androstene steroids produced metabolic profiles which suggested that the major role of the liver is phase II conjugation. Sulfoconjugated 16-androstene steroids included androstadienol, 5alpha-androstenone, 3beta-, 3alpha-androstenol, and possibly the hydroxylated metabolite of 5alpha-androstenone. It was determined that hydroxysteroid sulfotransferase (HST) is the likely candidate for the sulfoconjugation of the 16-androstene steroids within the liver. Despite the capacity of the hepatocytes to sulfoconjugate the 16-androstene steroids, the principle metabolites produced from incubations with 5alpha-androstenone, 3beta-, and 3alpha-androstenol were glucuronide conjugates, accounting for approximately 68% of all phase II metabolism. These findings underline the importance of steroid conjugation and suggest that hepatic metabolism of the 16-androstene steroids may influence the levels of 5alpha-androstenone present in the circulation, and thus, capable of accumulating in fat.

Androstenes↗
PubMed2005

Synthesis of free and sulphoconjugated 16-androstene steroids by the Leydig cells of the mature domestic boar.

This study examined the involvement of sulphoconjugation in the biosynthesis of the 16-androstene steroids in Leydig cells of the mature boar, since the formation of steroid sulphoconjugates can reduce the levels of these steroids that accumulate in fatty tissue. Leydig cells were purified from testes of mature male pigs and incubated with pregnenolone, or various individual 16-androstene steroids for 10 min, 1, 4 and 8h. Sulphoconjugated steroids were recovered by solid-phase extraction followed by solvolysis. Profiles of unconjugated and sulphoconjugated steroids were analysed by HPLC. Steroids present in the sulphoconjugated fractions were purified, derivatised as O-methoxime/trimethylsilyl ethers (MO-TMS), and subsequently identified using gas chromatography-mass spectrometry (GC-MS). The principal metabolite produced from incubations with pregnenolone, androstadienol, androstadienone and 5alpha-androstenone was 3beta-androstenol. 16-Androstene steroids that were sulphoconjugated included 5alpha-androstenone, 3beta-androstenol and 3alpha-androstenol. Approximately 70% of the total amount of each 16-androstene steroid was in its sulphoconjugated form after incubations for 4h or more. The finding that sulphoconjugated 5alpha-androstenone was present in large amounts suggests that this steroid may be converted from a 3-keto to a 3-enol form which is subsequently sulphoconjugated. These findings emphasise the need to consider the impact of sulphoconjugation of the 16-androstene steroids and their role in contributing to boar taint.

Androstanes↗
PubMed2005

Testicular sulfoconjugation of the 16-androstene steroids by hydroxysteroid sulfotransferase: its effect on the concentrations of 5alpha-androstenone in plasma and fat of the mature domestic boar.

This study examined the relationship between sulfoconjugation and the degree to which 5alpha-androstenone can accumulate in fat. Analysis of the unconjugated and sulfoconjugated fractions of peripheral plasma from 25 mature Yorkshire boars and testicular vein plasma from an additional 20 mature Yorkshire boars revealed that the majority of 5alpha-androstenone is present as a sulfoconjugate, reaching levels up to 69 +/- 4.3 and 72 +/- 6.2%, respectively, relative to its unconjugated form. The presence of this steroid in the sulfoconjugate fraction was confirmed by gas chromatography-mass spectrometry. Plasma concentrations of 5alpha-androstenone in the sulfoconjugate fraction were negatively correlated (r = -0.36; P < 0.01) with the concentrations of 5alpha-androstenone in fat. High concentrations of 5alpha-androstenone in the sulfate fraction were only associated with animals that had fat androstenone concentrations < 0.5 microg/g. In addition, there was a positive correlation (r = 0.31; P < 0.01) between the concentrations of unconjugated 5alpha-androstenone in plasma and 5alpha-androstenone in fat. These findings indicate that the levels of the sulfoconjugated form present in the peripheral plasma influence the accumulation of 5alpha-androstenone in fat. The specific sulfotransferase enzyme involved in sulfoconjugating these steroids was identified by incubating Leydig cells with specific sulfotransferase inhibitors for 8 h. It was discovered that the enzyme responsible for the sulfoconjugation of the 16-androstene steroids is hydroxysteroid sulfotransferase. Hydroxysteroid sulfotransferase may play a significant role in determining the levels of sulfated 16-androstene steroids present in plasma. The results of this study indicate that sulfoconjugation may serve to regulate the quantity of unconjugated 5alpha-androstenone present in the circulation and thus available for accumulation. Animals with a decreased ability to sulfoconjugate 5alpha-androstenone would have a subsequent increase in the levels of unconjugated 5alpha-androstenone in circulation, allowing for the accumulation of high levels in fat and thereby potentially leading to the development of boar taint.

Adipose Tissue↗
PubMed2001

Depression and self-reported functional status in older primary care patients.

OBJECTIVE: The authors' goal was to examine whether depression is associated with overreporting of functional disability. METHOD: The subjects were 304 patients 60 years old or older who were recruited from primary care settings. Measures included examiner ratings of depression diagnosis and medical burden and self-reported and examiner-rated functional assessments. Multiple regression techniques were used to determine the independent association of depression with self-reported function after examiner-rated function was added to the analysis as a covariate. RESULTS: Depression diagnosis was associated with poorer self-reported role functioning, whether the patient attributed the disability to physical or emotional causes. Depression was not independently associated with poorer self-reported physical functioning. CONCLUSIONS: Clinicians and researchers should recognize that depression can confound the self-reporting and attribution of functional disability.

Activities of Daily Living↗
PubMed2001

The effect of early postnatal treatment with a gonadotropin-releasing hormone agonist on the developmental profiles of testicular steroid hormones in the intact male pig.

Three studies examined the effects of early postnatal treatment with a GnRH agonist on plasma concentrations of testosterone, dehydroepian-drosterone sulfate, 16-androstene steroids in fat and salivary glands, androstenone in fat and plasma, and testicular development of intact male pigs. The first study involved 45 7-d-old pigs assigned to three treatment groups: 1) boars administered 100 microg/kg of Lupron depot, 2) boars administered 200 microg/kg of Lupron depot, and 3) control boars receiving a saline carrier. The second study involved 20 7-d-old pigs assigned to two treatments: daily injection of 200 microL of 0.5 mg/mL Lupron from d 7 to 35 and controls treated with saline. The third study involved a total of 100 animals assigned to 10 groups of 10 based on their age at slaughter. These groups were subdivided into one of two treatments: 1) boars injected with 200 microL of 0.5 mg/mL of Lupron from d 3 to 35 and 2) control boars injected with saline. Testicular steroid hormone concentrations in plasma decreased (P < 0.01) within 7 d of GnRH agonist treatment. Following cessation of treatment, steroid levels increased to control levels and remained constant until the final rise at 5 mo. Plasma testosterone levels in the 100 microg/kg depot treatment group were higher (P < 0.05) than that of the 200 microg/kg and control group at 164 d of age. There were no differences between treatments (P > 0.05) in testicular steroid hormone levels at the end of study 2 or 3. There were no differences (P > 0.05) in concentrations of 16-androstene steroids in salivary glands between any of the treatment groups at market weight in studies 1 and 2. Fat androstenone levels measured in the third study ranged between 0.6 microg/g and 4.2 microg/g at 7 to 28 d of age. Treatment with GnRH agonist decreased plasma steroid levels and testicular development; however, by d 60 testicular size and weight were at control levels and remained similar until 180 d of age. The results of these studies indicate that daily administration of a GnRH agonist significantly decreased testicular development and steroidogenesis only during treatment, but testis growth and steroidogenesis had returned to control levels by 60 d of age in male pigs. Suppression of the early postnatal rise in testicular steroid hormones did not affect growth performance or steroid hormone levels at 5 to 6 mo of age.

Adipose Tissue↗
PubMed2001

Early postnatal plasma concentrations of testicular steroid hormones, pubertal development, and carcass leanness as potential indicators of boar taint in market weight intact male pigs.

Testicular steroid hormone concentrations in plasma of early postnatal male pigs were compared with plasma steroid hormone concentrations and androstenone concentrations in the fat of pigs at market weight. Positive correlations were found between the concentrations of fat androstenone at market weight and the concentrations of plasma androstenone (r = 0.46; P < 0.01), estrone sulfate (r = 0.42; P < 0.01), and testosterone (r = 0.26; P < 0.05) at market weight. These correlations were not found in animals that had reached an advanced state of pubertal development as judged by high estrone sulfate concentrations in plasma. Significant correlations were observed between plasma testosterone concentrations at market weight and plasma concentrations of androstenone (r = 0.57; P < 0.05), and estrone sulfate (r = 0.49; P < 0.05) in early postnatal animals. However, concentrations of androstenone in the fat of market weight animals were not correlated with plasma concentrations of estrone sulfate, androstenone, or testosterone in early postnatal animals. Plasma concentrations of steroid hormones in early postnatal animals cannot, therefore, be used to predict the potential for boar taint in the same animals at market weight. In market weight animals, there was a negative correlation (r = -0.57; P < 0.01) between backfat thickness and concentrations of androstenone in fat. Animals were subsequently sorted according to backfat thickness into lean and fat groups of animals. There was a strong, negative correlation between back-fat thickness and androstenone concentrations in fat (r = -0.80; P < 0.01), as well as a positive correlation between plasma androstenone and concentrations of androstenone in fat (r = 0.42; P < 0.05) among the lean group of animals. This was not seen in the fat group of animals. This suggests that the accumulation of androstenone from plasma into fat may be affected by the leanness of the pig.

Adipose Tissue↗
PubMed2001

Vaginitis emphysematosa associated with an abnormal Pap smear.

Vaginitis emphysematosa is an uncommon inflammatory condition that is aetiologically linked to trichomonal or gardnerella infection, and has been associated with immunosuppressive disorders. The disease does not have deleterious sequelae and resolves on treating the underlying infection. We describe a case in which the disease predominantly affected the cervix leading to an abnormal pap smear and colposcopic investigation.

Colposcopy↗
PubMed1990

Testicular and paratesticular tumours at the University Hospital of the West Indies.

A review of tumours of the testis and paratesticular region diagnosed at the University Hospital of the West Indies over a 30-year period revealed 14 of the former and 22 of the latter. The testicular tumours were all malignant, with 50 per cent of them being germ-cell neoplasms. Seventeen of the 22 paratesticular tumours, (77.3%) were benign. The histological types, racial incidence and possible aetiological factors are discussed and compared with the findings of other series.

Adolescent↗