Hormonal Regulation of Glucocorticoid Inactivation and Reactivation in αT3-1 and LβT2 Gonadotroph Cells.

The regulation of reproductive function by glucocorticoids occurs at all levels of the hypothalamo-pituitary-gonadal axis. Within the pituitary, glucocorticoids have been shown to directly alter gene expression in gonadotrophs, indicating that these cell types are sensitive to regulation by the glucocorticoid receptor. Whilst the major glucocorticoid metabolising enzymes, 11β-hydroxysteroid dehydrogenase (11βHSD; HSD11B1 and HSD11B2), have been described in human pituitary adenomas, the activity of these enzymes within different pituitary cell types has not been reported.

Ovarian 11β-hydroxysteroid dehydrogenase (11βHSD) activity is suppressed in women with anovulatory polycystic ovary syndrome (PCOS): apparent role for ovarian androgens.

Context: Altered hepatic cortisol-cortisone metabolism by type 1 11β-hydroxysteroid dehydrogenase (11βHSD1) has previously been linked with polycystic ovary (PCO) syndrome (PCOS).

Objectives: Our objectives were to establish whether ovarian 11βHSD activities are also altered in PCOS and to determine whether any changes in ovarian cortisol metabolism might reflect exposure to elevated concentrations of insulin or androgens.

Design: Cortisol and cortisone concentrations were measured in follicular fluid aspirated from size-matched follicles dissected from normal, ovulatory, and anovulatory PCOs.

Regulation of glucocorticoid metabolism in the boar testis and caput epididymidis by the gonadotrophin-cAMP signalling pathway.

In target tissues, cortisol is metabolised by two 11β-hydroxysteroid dehydrogenase (11βHSD) isoenzymes, namely 11βHSD1 and 11βHSD2, both of which are co-expressed in the boar testis and reproductive tract. The present study has assessed whether cortisol-cortisone metabolism in boar testis and caput epididymidis can be regulated via the gonadotrophin-cAMP signalling pathway. 11βHSD activities were measured by using a radiometric conversion assay in static tissue culture.

The anti-epileptic drug valproic acid (VPA) inhibits steroidogenesis in bovine theca and granulosa cells in vitro.

Valproic acid (VPA) is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS)-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC) and granulosa (GC) cells maintained under conditions that preserve their 'follicular' phenotype.

Steroid synthesis by primary human keratinocytes; implications for skin disease.

Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol.

Expression and activities of 11betaHSD enzymes in the testes and reproductive tracts of sexually immature male pigs.

In light of studies implicating glucocorticoids in the control of testicular steroidogenesis and/or spermatogenesis, the objective of this study was to characterise the expression and activities of the 11beta-hydroxysteroid dehydrogenase (11betaHSD) enzymes in the testis and reproductive tract of the pre-pubertal pig. Although 11betaHSD1 and 11betaHSD2 mRNA transcripts and proteins were co-expressed in all regions of the reproductive tract, cortisol-cortisone inter-conversion was detectable in the testis, caput epididymidis and bulbourethral glands only. In homogenates of these 3 tissues, the apparent K(m) for NADP(+)- and NAD(+)-dependent 11beta-dehydrogenase activities ranged between 152-883 and 47-479 nmoll(-1), respectively.

Inactivation of glucocorticoids by 11beta-hydroxysteroid dehydrogenase enzymes increases during the meiotic maturation of porcine oocytes.

Recent reports have shown that glucocorticoids can modulate oocyte maturation in both teleost fish and mammals. Within potential target cells, the actions of physiological glucocorticoids are modulated by 11beta-hydroxysteroid dehydrogenase (HSD11B) isoenzymes that catalyse the interconversion of cortisol and cortisone. Hence, the objective of this study was to establish whether HSD11B enzymes mediate cortisol-cortisone metabolism in porcine oocytes and, if so, whether the rate of glucocorticoid metabolism changes during oocyte maturation.

Potential significance of physiological and pharmacological glucocorticoids in early pregnancy.

Background: Despite extensive studies of the developmental consequences of increased glucocorticoid exposure in mid- to late pregnancy, relatively little is known regarding the significance of glucocorticoids in early pregnancy. The objective of this review was to consider potential roles for this family of corticosteroids that might relate to early pregnancy.

Methods: Although this is a narrative review, 249 source articles addressing potential effects of glucocorticoids on aspects of early pregnancy and development (published between 1997 and 2007) were identified using a systematic literature search.

11Beta-hydroxysteroid dehydrogenase enzymes in the testis and male reproductive tract of the boar (Sus scrofa domestica) indicate local roles for glucocorticoids in male reproductive physiology.

11Beta-hydroxysteroid dehydrogenase (11betaHSD) enzymes modulate the target cell actions of corticosteroids by catalysing metabolism of the physiological glucocorticoid (GC), cortisol, to inert cortisone. Recent studies have implicated GCs in boar sperm apoptosis. Hence, the objective of this study was to characterise 11betaHSD enzyme expression and activities in the boar testis and reproductive tract.

Implication of cortisol and 11beta-hydroxysteroid dehydrogenase enzymes in the development of porcine (Sus scrofa domestica) ovarian follicles and cysts.

This study investigated cortisol inactivation by 11beta-hydroxysteroid dehydrogenase (11beta HSD) enzymes in porcine granulosa cells from antral follicles at different developmental stages and in ovarian cysts. In granulosa cells, cortisol oxidation increased threefold with antral follicle diameter (P < 0.001).

Role for prostaglandins in the regulation of type 1 11beta-hydroxysteroid dehydrogenase in human granulosa-lutein cells.

11beta-hydroxysteroid dehydrogenase (11betaHSD) enzymes regulate glucocorticoid availability in target tissues. 11betaHSD1 is the predominant isoenzyme expressed and active in human granulosa-lutein (hGL) cells. This study investigated the effects of pharmacological inhibitors of prostaglandin (PG) synthesis on 11betaHSD1 activities and expression in hGL cells.

Roles for prostaglandins in the steroidogenic response of human granulosa cells to high-density lipoproteins.

In human granulosa-lutein cells, high-density lipoproteins (HDL) can stimulate progesterone synthesis. The objective of the present study was to establish whether prostaglandins (PGs) participate in the steroidogenic response to HDL. Both HDL and apolipoprotein AI (ApoAI) stimulated concentration-dependent increases in PGE2, cAMP and progesterone accumulation.

Life after liquorice: the link between cortisol and conception.

Previous studies have reported both direct and indirect evidence correlating the probability of conception by IVF-embryo transfer with follicular metabolism of glucocorticoids by the enzyme 11 beta-hydroxysteroid dehydrogenase (11 betaHSD). To resolve disputes regarding the predictive value of measures of cortisol-cortisone interconversion, this study has focused on compounds present in follicular fluid that can regulate enzyme activities within the ovary. Follicular fluid contains both hydrophilic compounds that can stimulate and hydrophobic components that can inhibit the oxidation of cortisol to cortisone by 11 betaHSD.

Glucocorticoid metabolism and reproduction: a tale of two enzymes.

Within potential target cells, the actions of physiological glucocorticoids (cortisol and corticosterone) are modulated by isoforms of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). To date, two isoforms of 11 beta HSD have been cloned: 11 beta HSD1 acts predominantly as an NADP(H)-dependent reductase to generate active cortisol or corticosterone, and 11 beta HSD2 is a high affinity NAD(+)-dependent enzyme that catalyses the enzymatic inactivation of glucocorticoids. Whereas the regeneration of active glucocorticoids by 11 beta HSD1 has been implicated in the cellular mechanisms of pituitary function, ovulation and parturition, the enzymatic inactivation of cortisol and corticosterone by 11 beta HSD enzymes appears to be central to the protection of gonadal steroidogenesis, prevention of intra-uterine growth retardation, and lactation.

Binding of ovarian steroids to erythrocytes in patients with sickle cell disease; effects on cell sickling and osmotic fragility.

Ovarian steroids appear to influence the manifestations of sickle cell disease (SCD); oestrogens can adversely affect erythrocyte function, whereas progestogens may inhibit sickling and decrease the osmotic fragility of erythrocytes. The aims of the present studies were: (i) to characterise the binding of oestradiol and progesterone to erythrocytes from women with HbSS, HbSC and HbAA genotypes; (ii) to investigate whether steroids modulate susceptibility to sickling or osmotic fragility of HbSS and HbAA erythrocytes. Erythrocytes were incubated for 1h with [3H]-steroids at 4 and 37 degrees C.

Ovarian modulators of 11beta-hydroxysteroid dehydrogenase (11beta HSD) activity in follicular fluid from bovine and porcine large antral follicles and spontaneous ovarian cysts.

In the ovary, cortisol is oxidized to cortisone by 11beta-hydroxysteroid dehydrogenase (11betaHSD). The present study investigated whether follicular fluid (FF) from large antral follicles and spontaneous ovarian cysts, isolated from bovine and porcine ovaries, contained modulators of 11betaHSD activity. Whereas FF from antral follicles had no significant effect over 1 h on NADP+-dependent 11betaHSD activity in rat kidney homogenates, enzyme activity was inhibited by FF from bovine and porcine ovarian cysts (80.