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Biomedical subjects

J M Hutson

Publications and source records attributed to J M Hutson.

At least 145 records · Page 8Linked to original sources
PubMed1993

Testicular descent. II. Ontogeny and response to denervation of calcitonin gene-related peptide receptors in neonatal rat gubernaculum.

The gubernaculum guides inguino-scrotal testicular descent by migrating into the scrotum ahead of the testis. Calcitonin gene-related peptide (CGRP) is present in the genitofemoral nerve of the neonatal rat and stimulates gubernacular motility in vitro. In a previous study in vitro autoradiography demonstrated a distinctive distribution of binding sites for CGRP over the developing cremasteric muscle in the gubernaculum. Binding analysis using computerized densitometry revealed a single class of sites. This study aimed to characterize the ontogeny of CGRP receptors in the gubernaculum and their response to denervation. Gubernacular sections from neonatal male rats were incubated with [125I]human CGRP as well as a variety of unlabeled neuropeptides. The expression of CGRP receptors culminates during the first week after birth, when gubernacular migration actually occurs. Significantly higher binding capacities were found in the denervated gubernacula compared with those in controls, which suggests an upregulation of CGRP receptors as a result of the genitofemoral nerve denervation. These results are consistent with the hypothesis that CGRP released from the nerve acts directly on the developing cremaster via its own receptors, which have not been described previously in this tissue.

Aging↗
PubMed1993

Serum levels of mullerian inhibiting substance in boys throughout puberty and in the first two years of life.

Serum levels of Mullerian inhibiting substance (MIS) have been measured in 91 boys throughout normal pubertal development. MIS levels fell sharply after pubertal stage 1 and were mostly undetectable at pubertal stage 6. The relationship between MIS concentration and pubertal stage was similar when compared with age. Seven patients with precocious puberty and 12 with delayed puberty were also investigated and found to have MIS levels consistent with their degree of pubertal development. Precocious puberty was associated with MIS levels that were abnormally low for age, while delayed puberty resulted in persistence of high MIS levels. Serum MIS levels were also measured in 29 boys less than 2 yr of age undergoing minor surgery. High levels were found throughout this time period, which is consistent with previous reports. MIS levels appear to be inversely related to levels of gonadotropins, steroids, and inhibin, which fall in the first 2 yr of life and rise throughout puberty.

Adolescent↗
PubMed1993

The tammar wallaby (Macropus eugenii) and the Sprague-Dawley rat: comparative anatomy and physiology of inguinoscrotal testicular descent.

Inguinoscrotal testicular descent in the tammar wallaby (Macropus eugenii) and the Sprague-Dawley rat was studied by macroscopic dissection, histological evaluation and organ culture bioassay. In 3 or 4 d Sprague-Dawley rats (n = 10) the gubernacular tip bulged free from the surrounding tissues, particularly with the application of abdominal pressure. Microscopic examination revealed that only the body of the gubernaculum is connected posteriorly to the pubic region. In contrast, macroscopic dissection of male tammar wallabies (n = 17) revealed a densely adherent distal gubernacular attachment to the inside of the fibrous scrotal bulge while the body of the gubernaculum was less firmly attached. These attachments were present throughout the process of testicular descent, illustrating an important anatomical difference between these species. The gubernaculum from the tammar wallaby pouch young was studied in organ culture with rat calcitonin gene-related peptide for 4 d. Rhythmic gubernacular contractions similar to those documented previously in the rat were not observed. The hypothesis proposed in the rat for the control of inguinoscrotal gubernacular migration via the genitofemoral nerve and its neurotransmitters may not be applicable in marsupial mammals.

Animals↗
PubMed1992

Intrascrotal CGRP 8-37 causes a delay in testicular descent in mice.

The genitofemoral nerve is a key factor in the inguinoscrotal descent of the testis. The effect of androgens may be mediated via the central nervous system, which in turn secretes the neurotransmitter calcitonin gene-related peptide (CGRP) at the genitofemoral nerve endings, to cause testicular descent. The effect of endogenous CGRP was examined by weekly injections of a vehicle with or without synthetic antagonist (CGRP 8-37) into the developing scrotum of neonatal mice. The descent of the testis was delayed in the experimental group compared with the control group. At 2 weeks of age 43% of controls had descended testes compared with 0% of experimental animals. At 3 weeks of age 17% of experimentals still had undescended testes, whereas all testes were descended in controls. At 4 weeks 3 testes remained undescended in the experimental group. It is concluded that the CGRP antagonist can retard testicular descent. This result is consistent with the hypothesis that CGRP is an important intermediary in testicular descent.

Animals↗
PubMed1992

Demonstration of calcitonin gene-related peptide receptors in the gubernaculum by computerized densitometry.

The gubernaculum appears to guide inguinoscrotal testicular descent by migration into the scrotum ahead of the testis. Calcitonin gene-related peptide (CGRP) has been found in the scrotal branches of the genitofemoral nerve of neonatal rats, and is known to stimulate gubernacular motility in vitro. This study aimed to identify CGRP receptors in the gubernaculum, which should be present if CGRP mediates gubernacular migration toward the scrotum. Gubernacular sections from neonatal male rats were incubated with [125I]-human CGRP as well as a variety of unlabeled neuropeptides. By using computerized densitometry, the quantitation of CGRP binding derived from in vitro autoradiography demonstrated a distinctive distribution of binding sites for CGRP over the developing cremasteric muscle in the gubernaculum. The binding analysis showed a single class of sites with a dissociation constant (Kd) of 2.13 nmol/L and a receptor density of 27.4 fmol/mg polymer. These results endorse the hypothesis that CGRP released from the nerve acts directly on the cremaster via its own receptors, which have not been described previously.

Absorptiometry, Photon↗
PubMed1992

Testicular descent. III. The neonatal mouse gubernaculum shows rhythmic contraction in organ culture in response to calcitonin gene-related peptide.

The effects of calcitonin gene-related peptide (CGRP) and CGRP 8-37 on the neonatal mouse gubernaculum were examined in organ culture, with the aim of seeing whether CGRP has a direct effect on the gubernaculum. A total of 440 gubernacula were studied. Two hundred and fifty gubernacula were treated with CGRP in concentrations ranging from 0-714 nM/liter. With increasing doses of CGRP the percentage of gubernacula showing vigorous contraction increased from 18-50%. The total percentage of gubernacula showing any form of contraction increased from 76-96%. One hundred and fifty gubernacula were exposed to the CGRP analog CGRP 8-37. Increasing concentrations of CGRP 8-37 from 179-714 nM/liter decreased the rate of vigorous contraction from 18-4%. The percentage of gubernacula showing any degree of contraction decreased from 76-14%. Forty gubernacula removed from testicular feminization (TFM) mice were exposed to varying concentrations of CGRP. In the absence of exogenous CGRP no contractility was observed. By contrast, in the presence of CGRP the gubernacula showed vigorous contractility increasing from 38-90%. The total number of gubernacula showing contraction increased from 75-100%. These studies demonstrated that the neonatal mouse gubernaculum exhibits a high level of endogenous contractility, which can be enhanced in a dose responsive manner with exogenous CGRP. CGRP 8-37 caused a dose responsive inhibition. The androgen-insensitive gubernaculum from the TFM mouse showed no endogenous contraction, but on exposure to CGRP showed an enhanced rate of contractility. These results are consistent with the hypothesis that androgens may control gubernacular migration indirectly via release of CGRP from the genitofemoral nerve in the inguinoscrotal region. The failure of gubernacular motility in vitro and migration in vivo in the TFM mouse may indicate lack of CGRP release from the genitofemoral nerve.

Androgen-Insensitivity Syndrome↗
PubMed1992

Prospective evaluation of the contraction stress and nonstress tests in the management of post-term pregnancy.

Eight hundred and nineteen patients were evaluated at greater than or equal to 280 days' gestation. All patients underwent nonstress test (NST) and breast stimulation to induce contraction stress test (CST), except where contraindicated. If CST was nonqualifying (less than three contractions per ten minutes), Pitocin (oxytocin) was used to complete the CST if there was a nonreactive NST. Delivery was instituted for any abnormal CST, even with a reactive NST, based on the last test within seven days of delivery. There were 747 reactive NST and 72 nonreactive NST. Breast stimulation for CST was done in 655 instances--315 (48 per cent) had nonqualifying CST and 340 (52 per cent) had qualifying CST. There was an increased incidence of induction in the nonqualifying CST group and abnormal CST group. There were no statistically significant differences in perinatal outcomes in the group with reactive NST, irrespective of the CST result. There were no antepartum fetal deaths.

Evaluation Studies as Topic↗
PubMed1991

The gubernaculum shows rhythmic contractility and active movement during testicular descent.

Androgens are postulated to act indirectly on the gubernaculum via the genitofermoral nerve, which contains specific neuropeptide transmitters. We examined gubernacula in vitro and in vivo to see if these neuropeptides affected the gubernacular development directly. Gubernacula (n = 272) from male rats (aged 0 to 3 days) were incubated in organ culture with various different neurotransmitters. The cultures were examined daily with a dissecting microscope connected to a video camera and tape. Some rats were anaesthetized and the inguinoscrotal skin was excised to expose the gubernacula for in vivo video recording. Of 181 gubernacula treated with calcitonin gene-related peptide (CGRP) at concentrations of 7 to 714 nmol/L, 92 showed rhythmic contractions. The number of responsive gubernacula was proportional to CGRP concentrations (r = .685). This compared with 9 of 40 gubernacula treated with vasoactive intestinal peptide and 2 of 25 controls. Neither female gubernacula, skeletal muscle, nor umbilical cord showed CGRP-induced contractions. Gubernacula in vivo showed vigorous contractility and serpentine movements, which were accentuated by increased intraabdominal pressure. These studies demonstrate the gubernaculum to be highly motile during testicular descent. Rhythmic contractions suggest the presence of possible smooth muscle-like components that may be modulated by CGRP release from the genitofemoral nerve.

Acetylcholine↗
PubMed1991

Serum levels of Mullerian inhibiting substance in boys with cryptorchidism.

Serum levels of Mullerian inhibiting substance (MIS) were measured in boys with cryptorchidism (n = 104) and paired, age-matched controls (n = 104) using an enzyme immunoassay. Control MIS levels were high during the first year of life with a peak level at 4 to 12 months, subsequently diminishing with age. MIS levels in patients with undescended testes also declined with age, although a surge was not found in the first year. Mean MIS concentration of cryptorchid boys was significantly lower than controls (P less than .001). There was a significant reduction of the mean MIS level in children with bilateral cryptorchidism compared with those with unilateral undescended testis (P less than .05). These differences might support the hypothesis that MIS initiates transabdominal testicular descent. However, because most undescended testes are probably the result of anatomical or functional abnormalities during transinguinal testicular descent, differences in MIS levels more likely result from secondary testicular degeneration. In the future, MIS immunoassay should play an important role in the investigation of gonadal function in boys with various genital disorders, including cryptorchidism.

Adolescent↗
PubMed1991

The anatomy of the female gubernaculum is different from the male.

The round ligament, or female gubernaculum, is believed to terminate in the labium majorum. In the 30-week old male foetus, however, the gubernaculum ends outside the external ring, later migrating into the scrotum under androgenic control. We studied the round ligament anatomy in the female to define its position and to see whether it reaches the labium. Post-mortem examination of 10 females (0-11 years), dying of non-genital disorders defined the anatomy of the round ligament by dissection and photography. The round ligament ended just outside the external ring in all females, with neither attachment, nor extension, to the caudal labium. A short processus vaginalis (canal of Nuck) was found in 1 patient. This study showed that the round ligament fails to reach the caudal labium, which is the homologue of the hemiscrotum. The migration of the male gubernaculum into the scrotum to enable descent of the testis does not occur in females. The description of the round ligament in standard textbooks of anatomy should be amended.

Child↗
PubMed1990

Longitudinal study of the renin-angiotensin-aldosterone system in hypertensive pregnant women: deviations related to the development of superimposed preeclampsia.

A prospective longitudinal study of 25 pregnant women (30 pregnancies) with chronic hypertension, a group prone to development of preeclampsia, was conducted to explore the relationship between the renin-angiotensin-aldosterone system and the development of superimposed preeclampsia. In women with chronic hypertension in whom preeclampsia did not develop (17 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated, beginning in the first trimester and continuing throughout pregnancy as found previously in normotensive pregnant women (n = 58). Plasma estradiol and progesterone levels also increased progressively. In women with chronic hypertension in whom preeclampsia developed (13 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated in the first trimester as in the other groups. However, later in pregnancy significant differences were observed. Blood pressure began to rise in the second trimester. Initially the renin-angiotensin-aldosterone system remained stimulated, but in the early third trimester, when preeclampsia was diagnosed, plasma renin activity and urine aldosterone excretion decreased, and atrial natriuretic factor increased. These data provide information that may be useful in the recognition of superimposed preeclampsia, and in the investigation of its pathogenesis.

Adult↗
PubMed1990

Serum levels of müllerian inhibiting substance in boys from birth to 18 years, as determined by enzyme immunoassay.

An enzyme immunoassay was set up with the aim of determining the serum levels of Müllerian inhibiting substance (MIS) during childhood. A monoclonal antibody against purified bovine MIS was combined with a polyclonal antibody against recombinant human MIS to make a sandwich assay. This assay detected MIS in human serum within the following criteria. Ninety-eight boys, aged between birth and 18 yr, who had been admitted to the Royal Children's Hospital, were included. MIS levels were measured in samples taken for biochemical screening of unrelated disorders. MIS was detected in the serum up to 16 yr of age, but was low beyond 12 yr and undetectable at 18 yr. High MIS levels were found at 4-12 months, consistent with MIS having an important function at this time. Germ cells undergo an important transformation from gonocytes to spermatogonia at the same time as the MIS levels peak, suggesting a possible function for MIS.

Adolescent↗