Search Results

You are looking at 1 - 5 of 5 items for

  • Author: S Pearce x
  • Refine by Access: All content x
Clear All Modify Search
Restricted access

P. J. O'Shaughnessy, S. Pearce, and M. A. Mannan


It has been proposed that changes in steroidogenesis which occur during early development of the corpus luteum may be due to increased availability of lipoproteins. Bovine follicular fluid, however, contains significant amounts of high-density lipoprotein (HDL), and granulosa cells are exposed to this lipoprotein before ovulation. To determine whether bovine granulosa cells can utilize HDL the effects of this lipoprotein on freshly isolated, non-luteinized granulosa cells and on granulosa cells undergoing luteinization in serum-free culture were examined. Cells were isolated from non-atretic, antral follicles and cultured for 12 h in 10% (v/v) lipoprotein-deficient serum to allow cell attachment. After this time cells were cultured in serum-free medium. During culture the cells underwent functional luteinization as assessed by an increase in basal progesterone output (9·6-fold in 7 days) which was associated with a marked increase in activity of cholesterol side-chain cleavage and loss of aromatase activity. Dibutyryl cyclic AMP (dbcAMP) increased basal production of progesterone about twofold but HDL alone had no effect. Addition of HDL plus dbcAMP, in contrast, caused a very marked stimulation (up to ten times) of basal steroidogenesis. This trophic effect of HDL and dbcAMP lasted at least 2 weeks. Activity of cholesterol side-chain cleavage was stimulated (threefold over basal) by dbcAMP during culture but HDL was without effect, alone or with dbcAMP.

Addition of HDL (in the presence or absence of dbcAMP) to freshly isolated granulosa cells had no significant stimulatory effect on progesterone production over 12 h in six experiments, and in two of these experiments a significant inhibitory effect was seen. Incubation with 22R-hydroxycholesterol, in contrast, caused a marked stimulation of progesterone production, indicating that the steroidogenic capacity of the cells was not already saturated. Results presented here suggest that bovine granulosa cells are able to utilize HDL for steroidogenesis only after luteinization. The massive secretion of progesterone by luteinized granulosa cells which occurs in the presence of HDL suggests that this lipoprotein is very important in the development and maintenance of luteal cell function in cattle.

Journal of Endocrinology (1990) 124, 255–260

Free access

ME Symonds, A Mostyn, S Pearce, H Budge, and T Stephenson

In the fetus, adipose tIssue comprises both brown and white adipocytes for which brown fat is characterised as possessing the unique uncoupling protein (UCP)1. The dual characteristics of fetal fat reflect its critical role at birth in providing lipid that is mobilised rapidly following activation of UCP1 upon cold exposure to the extra-uterine environment. A key stage in the maturation of fetal fat is the gradual rise in the abundance of UCP1. For species with a mature hypothalamic-pituitary axis at birth there is a gradual increase in the amount and activity of UCP1 during late gestation, in conjunction with an increase in the plasma concentrations of catecholamines, thyroid hormones, cortisol, leptin and prolactin. These may act individually, or in combination, to promote UCP1 expression and, following the post-partum surge in each hormone, UCP1 abundance attains maximal amounts.Adipose tIssue grows in the fetus at a much lower rate than in the postnatal period. However, its growth is under marked nutritional constraints and, in contrast to many other fetal organs that are unaffected by nutritional manipulation, fat mass can be significantly altered by changes in maternal and, therefore, fetal nutrition. Fat deposition in the fetus is enhanced during late gestation following a previous period of nutrient restriction up to mid gestation. This is accompanied by increased mRNA abundance for the receptors of IGF-I and IGF-II. In contrast, increasing maternal nutrition in late gestation results in less adipose tIssue deposition but enhanced UCP1 abundance. The pronounced nutritional sensitivity of fetal adipose tIssue to both increased and decreased maternal nutrition may explain why the consequences of an adverse nutritional environment persist into later life.

Free access

A Mostyn, S Pearce, H Budge, M Elmes, AJ Forhead, AL Fowden, T Stephenson, and ME Symonds

The present study examined the extent to which the late gestation rise in fetal plasma cortisol influenced adipose tIssue development in the fetus. The effect of cortisol on the abundance of adipose tIssue mitochondrial proteins on both the inner (i.e. uncoupling protein (UCP)1) and outer (i.e. voltage-dependent anion channel (VDAC)) mitochondrial membrane, together with the long and short forms of the prolactin receptor (PRLR) protein and leptin mRNA was determined. Perirenal adipose tIssue was sampled from ovine fetuses to which (i) cortisol (2-3 mg/day for 5 days) or saline was infused up to 127-130 days of gestation, and (ii) adrenalectomised and intact controls at between 142 and 145 days of gestation (term=148 days). UCP1 protein abundance was significantly lower in adrenalectomised fetuses compared with age-matched controls, and UCP1 was increased by cortisol infusion and with gestational age. Adrenalectomy reduced the concentration of the long form of PRLR, although this effect was only significant for the highest molecular weight isoform. In contrast, neither the short form of PRLR, VDAC protein abundance or leptin mRNA expression was significantly affected by gestational age or cortisol status. Fetal plasma triiodothyronine concentrations were increased by cortisol and with gestational age, an affect abolished by adrenalectomy. When all treatment groups were combined, both plasma cortisol and triiodothyronine concentrations were positively correlated with UCP1 protein abundance. In conclusion, an intact adrenal is necessary for the late gestation rise in UCP1 protein abundance but cortisol does not appear to have a major stimulatory role in promoting leptin expression in fetal adipose tIssue. It remains to be established whether effects on UCP1 protein are directly regulated by cortisol alone or mediated by other anabolic fetal hormones such as triiodothyronine.

Restricted access

A. R. Goldsmith, W. E. Ivings, A. S. Pearce-Kelly, D. M. Parry, G. Plowman, T. J. Nicholls, and B. K. Follett


The development of the reproductive system was studied in juvenile starlings during the acquisition of photosensitivity, the attainment of sexual maturation after photostimulation and the subsequent onset of photorefractoriness, using immunohistochemistry for LHRH and radioimmunoassay measurements of hypothalamic, pituitary and plasma hormone concentrations. The first stage of sexual development induced by exposure of photorefractory immature starlings to short days (8 h light:16 h darkness; 8L:16D) was characterized by a decrease in pituitary prolactin content within 1 week and an increase in hypothalamic LHRH content, in the size of the LHRH perikarya and in the intensity of immunostaining in the median eminence in 4–6 weeks. Sexual maturation occurring after exposure to long days (18L:6D) was associated with further increases in LHRH content and cell size, and increases in LH and prolactin concentrations. During testicular regression, LHRH perikarya were reduced in size and staining intensity but LHRH immunostaining in the median eminence and content in the hypothalamus remained high until gonadal regression was almost complete. Prolactin levels were maximal during testicular regression. These results suggest that gonadal regression is initiated by a reduction in LHRH synthesis and possibly, in addition, an external inhibitory influence on LHRH release. Hypothalamic LHRH content eventually declined and LHRH immunostaining in the median eminence was much reduced in fully photorefractory starlings maintained under long days.

Journal of Endocrinology (1989) 122, 255–268

Free access

S Pearce, H Budge, A Mostyn, E Genever, R Webb, P Ingleton, A M Walker, M E Symonds, and T Stephenson

A primary role of the prolactin receptor (PRLR) during fetal and postnatal development has been suggested to be the regulation of uncoupling protein (UCP) expression. We, therefore, determined whether: (1) the rate of loss of UCP1 from brown adipose tissue after birth was paralleled by the disappearance of PRLR; and (2) administration of either pituitary extract prolactin (PRL) containing a mixture of posttranslationally modified forms or its pseudophosphorylated form (S179D PRL) improved thermoregulation and UCP1 function over the first week of neonatal life. PRLR abundance was greatest in adipose tissue 6 h after birth before declining up to 30 days of age, a trend mirrored by first a gain and then a loss of UCP1. In contrast, in the liver – which does not possess UCPs –a postnatal decline in PRLR was not observed. Administration of PRL resulted in an acute increase in colonic temperature in conjunction with increased plasma concentrations of non-esterified fatty acids and, as a result, the normal postnatal decline in body temperature was delayed. S179D PRL at lower concentrations resulted in a transient rise in colonic temperature at both 2 and 6 days of age. In conclusion, we have demonstrated a close relationship between the ontogeny of UCP1 and the PRLR. Exogenous PRL administration elicits a thermogenic effect suggesting an important role for the PRLR in regulating UCP1 function.