In this study we have applied the technique of hypothalamo-pituitary disconnection (HPD) to the fetal sheep at 108–112 days of gestation. The pituitary is surgically disconnected from the hypothalamus by the removal of the neural component of the median eminence above the level of the portal circulation. This procedure results in the complete disconnection of the pituitary from the hypothalamus. After HPD, the lactotroph response to the dopamine antagonist chlorpromazine was significantly reduced (p < 0.005) indicating the functional isolation of the pituitary gland from the hypothalamus. The increase in plasma prolactin in response to exogenous thyrotrophin-releasing factor was maintained following HPD. HPD resulted in the complete atrophy of the pars nervosa. At 132–135 days of gestation after HPD there was no change in the volume or appearance of the pars distalis; small infarcts were observed in the pars distalis of some HPD fetuses, but these occupied less than 1% of the volume of the anterior lobe of the pituitary. There was a significant increase (p < 0.05) in the volume of the pars intermedia after HPD. Gestation was prolonged for at least 8 days beyond normal term following HPD, indicating that the processes integral to the initiation of parturition at term had been disrupted. We conclude that HPD provides a good in vivo model for the investigation of the activity of the isolated pituitary gland, and for the examination of the role of neuroendocrine mechanisms in fetal sheep development in the latter third of gestation.
Abstract. The effect of ACTH administration for 1—5 days on the morphology and steroidogenic capability of sheep adrenal tissue has been examined. During this period of treatment there was a gradual decline in the in vitro conversion of 3H-labelled precursors to products of solely zona glomerulosa origin (aldosterone and 18-hydroxycorticosterone) while conversion to products of zona fasciculata origin (17-hydroxyprogesterone, 11-deoxycortisol and cortisol) was stimulated throughout. Conversion to DOC, 18-hydroxydeoxycorticosterone and corticosterone (steroids produced by both the zona glomerulosa and the zona fasciculata) declined after initial stimulation. Within 2—3 days of the commencement of treatment, the zona glomerulosa showed a progressive decrease in cell number associated with disruption of cords and cell separation. Ultrastructurally, it was found that typical zona glomerulosa cells had almost disappeared. The majority of residual cells in this area had a structure intermediate between zona glomerulosa and zona fasciculata cells. The similarity in time-course of the alterations in both the morphological and biosynthetic characteristics suggests that the decline in aldosterone output caused by ACTH administration to sheep results from the loss of adrenal zona glomerulosa cells, predominantly due to selective cellular degeneration.
The cortex of sheep foetal adrenal glands from 25 days gestation until newborn (term equals 147 ± 3 days) were examined by light and electron microscopy. Three stages of development are of particular importance in relating structure to function: 1) from 35 to 60 days, 2) from 60 to 120 days and 3) from 120 days to term. Between 35 and 60 days one cortical cell type predominated. It contained mitochondria with lamellar and vesicular cristae, scattered long strands of granular endoplasmic reticulum and only small amounts of smooth endoplasmic reticulum. After about 60 days two zones were apparent in the cortex and chromaffin cells became concentrated in the medulla. After 80 days the outer zone contained cells which resembled mature zona glomerulosa cells and the cells in the inner zone remained like those seen between 35 and 60 days, except they contained even less smooth endoplasmic reticulum. However, after about 90 days a small number of deep inner zone cells contained mitochondria with vesicular cristae which thus resemble mitochondria in the mature zona fasciculata. From about 120 days there was an increase in the number of cells in the inner zone that contained mitochondria with vesicular cristae. These cells also contained substantial quantities of smooth endoplasmic reticulum. At term most inner zone cells have this mature appearance. Thus there is no "foetal cortex" in the sheep analogous to that found in human adrenal development, i. e. there is no prominent zone of cells containing large amounts of smooth endoplasmic reticulum which is present throughout most of the foetal period of development, and which regresses at birth. The structure of the cells present between 35 and 60 days was unexpected because it has been shown previously that sheep foetal adrenals of this age are capable of producing relatively large quantities of steroid hormones. However, the appearance of cells resembling mature zona glomerulosa cells at about 80 days correlates with the previously demonstrated ability of sheep adrenal glands of this age to produce relatively large quantities of aldosterone. The rapid development of numbers of mature cells in the last 3 weeks of gestation correlates with the previously described ability of near term sheep foetal adrenals to produce very large quantities of steroid hormones.
Objective: To determine the prevalence and clonality of non‐toxigenic Corynebacterium diphtheriae biovar gravis in a community with two cases of endocarditis caused by this organism. Setting: A Koorie (Aboriginal) community in Gippsland, eastern Victoria, in 1994. Methods: Nose and throat swabs were collected from 359 community contacts of the cases and cultured for C. diphtheriae. Strains isolated from the contacts were compared by pulsed‐field gel electrophoresis (after digestion with Sma1, Not1 and Sfi1) with those from the invasive cases in the same community, another invasive case in Victoria, a cluster of invasive cases in New South Wales (NSW) (1990–1991), and other stored strains isolated from skin ulcers and sore throats. Results: Non‐toxigenic strains of C. diphtheriae biovar gravis were isolated from throat swabs of five of the case contacts. Uniform DNA patterns were found for the two community cases, the other Victorian case, nine of ten isolates from NSW, and the five throat isolates from case contacts. Conclusion: An invasive clone of C. diphtheriae biovar gravis appears to have been responsible for the three Victorian cases of endocarditis. It was also present among case contacts and responsible for previous invasive cases in NSW. Prophylactic treatment should be considered for clearly defined contacts in all instances where C. diphtheriae is isolated from a normally sterile site, regardless of the toxigenic nature of the strain.
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