Biomedical subjects

R J Rodgers

Publications and source records attributed to R J Rodgers.

At least 145 records · Page 8Linked to original sources

PubMed1989

Prevention of the analgesic consequences of social defeat in male mice by 5-HT1A anxiolytics, buspirone, gepirone and ipsapirone.

Behavioural and pharmacological studies have suggested that anxiety may be an important factor in the initiation of non-opioid analgesia in defeated male mice. In the present study, the effects of three 5-HT1A anxiolytics (buspirone, ipsapirone and gepirone) on basal nociception and defeat analgesia were examined. Results show that the analgesic consequences of social defeat were potently blocked by all three compounds, with a rank-order potency (minimum effective doses) of ipsapirone (0.05 mg/kg) greater than gepirone (0.1 mg/kg) greater than buspirone (0.5 mg/kg). These inhibitory effects on defeat analgesia were observed in the absence of intrinsic activity on basal nociception (tail-flick assay). When administered alone, (-)pindolol produced biphasic effects on defeat analgesia with enhancement at 0.5 mg/kg and inhibition at 5.0 mg/kg. Lower doses of (-)pindolol (0.05 and 0.25 mg/kg) which did not affect defeat analgesia when administered alone, totally blocked the inhibitory effects of ipsapirone (0.5 mg/kg). Data are discussed in relation to the involvement of 5-HT1A receptor mechanisms in this adaptive form of pain inhibition.

Analgesia↗

PubMed1989

Differential effects of the CCK antagonist, MK-329, on analgesia induced by morphine, social conflict (opioid) and defeat experience (non-opioid) in male mice.

The effects of the potent and selective CCK antagonist, MK-329, on morphine- and environmentally-induced analgesia were examined in male mice. The results show that MK-329 (0.005-0.1 mg/kg) was devoid of intrinsic analgetic activity on the mouse tail-flick assay and, over the dose range 0.01-0.5 mg/kg, was without significant effect upon non-opioid analgesia, induced by defeat experience. However, opposite effects of MK-329 on analgesia induced by morphine and opioid-mediated social conflict analgesia were observed. That is, 0.05-0.01 mg/kg MK-329 (but not smaller doses) enhanced, and modestly prolonged, the duration of analgesia induced by 5 mg/kg morphine. In direct contrast, 0.0001-0.5 mg/kg of the CCK antagonist very potently inhibited opioid-typical analgesia in mice exposed to intense conspecific attack. In the latter studies, a residual short-lasting analgesia in mice, treated with MK-329, was found to be resistant to naloxone (5 mg/kg), indicating its non-opioid nature and confirming the lack of effect of the CCK antagonist on opioid-independent analgesia. It is suggested that the variable effects of MK-329 on morphine-induced and opioid-mediated social conflict analgesia may reflect differential, dose-dependent effects at CCK-B and CCK-A sites respectively, a proposal consistent with the 500-fold potency difference observed between the two models.

Analgesia↗

PubMed1989

The inhibitory effects of fluprazine on parental aggression in female mice are dependent upon intruder sex.

Lactating resident mice respond differently to male and female intruder conspecifics, showing defensive attack towards the former and offensive attack towards the latter. The effects of fluprazine (1-5 mg/kg) on this differential response pattern have been assessed. Although fluprazine increased the latencies of attack on male intruders, a very much more potent inhibitory effect was observed on attacks directed towards female intruders. Fluprazine also modestly reduced social investigation of female intruders and increased nest-oriented behaviour irrespective of the intruder's sex. As the pattern of attack on intruders, exploration, fear responses and maintenance behaviour all remained largely intact under drug treatment, it seems unlikely that the drug's inhibitory action on attack involves fear potentiation and/or olfactory impairment. It is suggested that the greater sensitivity of offensive attack to the inhibitory actions of fluprazine may reflect the relative degree of threat to resident parental investment posed by male and female conspecific intruders.

Aggression↗

PubMed1989

Inhibin mRNAs in ovine and bovine ovarian follicles and corpora lutea throughout the estrous cycle and gestation.

Follicles and corpora lutea were dissected from ovine and bovine ovaries and the RNA extracted and subjected to Northern blot analyses for alpha- and beta A-inhibin mRNAs, using bovine cDNA and cRNA probes. A cDNA probe detecting mRNA for cholesterol side-chain cleavage cytochrome P-450 (P-450scc) was used as a positive control. In cattle, alpha- and beta A-inhibin mRNAs were not detected in ovarian stroma, which could potentially have contained follicles up to 0.5 mm in diameter. Inhibin-alpha and -beta A mRNAs were detected in bovine antral follicles but after ovulation, the relative levels of alpha- and beta A-inhibin mRNAs declined and were undetectable in mature fully developed cyclic corpora lutea and in pregnancy corpora lutea from early to late gestation of the cow. In sheep, alpha- and beta A-inhibin mRNAs were detected in a pool of antral follicles but not in cyclic or pregnancy corpora lutea, which did contain P-450scc mRNA. It is concluded that in cattle and sheep, follicles and not mature corpora lutea are the ovarian source of inhibin.

Animals↗

PubMed1989

Cellular composition of the cyclic corpus luteum of the cow.

The cellular composition of CL from 6 cows on approximately Day 12 of the oestrous cycle, after synchronization with cloprostenol, was studied by ultrastructural morphometry. Point-count measurements of volume density (mean +/- s.d.) showed that large luteal cells occupied 40.2 +/- 7.0% of the luteal tissue, and small luteal cells 27.7 +/- 6.3%. Of the total of 393.4 +/- 52.0 x 10(3) cells per mm3 of luteal tissue, large luteal cells made up only 3.5% and small luteal cells 26.7%, a ratio of 1:7.6. Endothelial cells/pericytes, at 52.3%, were the most numerous cell type. The mean volume per large luteal cell was 29.6 +/- 6.3 x 10(3) microns 3, while that of small luteal cells was 2.7 +/- 0.4 x 10(3) microns 3. In spherical form, these volumes would represent mean diameters of 38.4 microns and 17.2 microns respectively, and are consistent with published measurements on dispersed luteal cells. However, the values for cell numbers are much higher than published values based on luteal tissue dispersion, suggesting that dispersion may result in substantial and possibly selective losses of luteal cells.

Animals↗

PubMed1988

Blockade of non-opioid analgesia in intruder mice by selective neuronal and non-neuronal benzodiazepine recognition site ligands.

In male mice, the biologically significant experience of social defeat is associated with an acute non-opioid form of analgesia. Recent studies have shown that this reaction is sensitive to certain benzodiazepine receptor ligands but is unaffected by others. The present experiments were designed to assess the possibility that activity at "non-neuronal" benzodiazepine binding sites might account for this unusual pharmacological profile. Our results show that defeat analgesia was blocked by clonazepam (0.06-3 mg/kg), Ro05-4864 (2.5-20 mg/kg), Ro05-5115 (20 mg/kg), PK11195 (5-20 mg/kg) and PK14067 (10-20 mg/kg). Furthermore, when given in combination, subthreshold doses of PK11195 (2.5 mg/kg) and clonazepam (0.03 mg/kg) totally prevented defeat analgesia. All of these effects were observed in the absence of intrinsic activity on basal nociception. Together with earlier findings, current data imply that inhibition of defeat analgesia by ligands for neuronal and/or non-neuronal benzodiazepine recognition sites is most probably unrelated to their activity at these sites. Alternative explanations for the overall patterns of results are considered.

Aggression↗

PubMed1988

Potent inhibition of non-opioid defeat analgesia in male mice by benzodiazepine antagonist Ro15-3505.

In male mice, defeat in social encounters is associated with an acute non-opioid analgesia, a reaction that may also be seen in response to the scent of a territorial conspecific. As this form of pain inhibition is blocked by diazepam and Ro15-1788, benzodiazepine receptor mediation has been proposed. To further test this hypothesis, the effects of a novel benzodiazepine receptor antagonist (Ro15-3505; 0.625-20 mg/kg) on basal nociception and defeat analgesia have been examined. Results show that, although devoid of intrinsic activity on the mouse tail-flick assay, Ro15-3505 totally blocks the analgesic consequences of defeat at doses above 1.25 mg/kg. Despite certain inconsistencies in the literature, present data provide further support for benzodiazepine receptor mediation of this ecologically-relevant form of pain inhibition.

Animals↗

PubMed1988

'Taming' of wild rats (Rattus rattus) by 5HT1A agonists buspirone and gepirone.

A battery of tests designed to elicit reactions to a variety of nonpainful threat stimuli was used to study the effects of the 5HT1A agonists buspirone (5-20 mg/kg), and gepirone (5-20 mg/kg) on the defensive repertoire of wild Rattus rattus. These two compounds produced very similar patterns of results on the test battery, with gepirone generally more effective: Both compounds failed to interfere with either spontaneous motor activity or avoidance/flight to an approaching experimenter. However, both reduced defensive reactivity to proximal threat stimuli, increasing passive contacts with the experimenter in an inescapable situation and reducing "proximal" defensive reactions: jump/flinch reactions to dorsal contact, and, boxing, and biting to a number of threat stimuli. Defensive threat vocalizations and jump attacks were also reduced, but less consistently, as was the experimenter's rating of subject's defensiveness to being picked up. This pattern of results suggested specific "taming" effects of buspirone and, especially, gepirone on defensive reactions. In combination with findings indicating somewhat different (benzodiazepines) to very different (ethanol) profiles for other anxiolytics in the same test battery, these results suggest that the Defense Test Battery may be capable of providing behavioural differentiation among various classes of anxiolytics.

Animals↗

PubMed1988

Actions of cyclic adenosine monophosphate on the cytodifferentiation of ovarian cells: studies in cultured swine granulosa cells using a novel exogenous adenylate cyclase from Bordetella pertussis.

The regulation by cAMP of cholesterol side-chain cleavage activity and the synthesis of immunoisolated cytochrome P-450scc and adrenodoxin proteins was investigated in primary cultures of swine ovarian (granulosa) cells. Administration of a novel adenylate cyclase toxin isolated from Bordetella pertussis increased granulosa-cell cAMP accumulation up to 200-fold over basal. These effects were additive with those of FSH, forskolin, and cholera toxin. In contrast, bacterial extracts BP 347 and BP 348 from mutant strains of B. pertussis that lack either all virulent factors or the adenylate cyclase toxin and hemolysin were devoid of effect. Granulosa-cell cAMP accumulation supported by active bacterial adenylate cyclase was accompanied by 2- to 11-fold, time-dependent increases in [35S]methionine incorporation into immunospecific cytochrome P-450scc and adrenodoxin. These increases in the synthesis of cholesterol side-chain cleavage proteins were associated with enhanced pregnenolone production in response to exogenous sterol substrate, 25-hydroxycholesterol, and augmented progesterone secretion both in the absence and presence of exogenous lipoprotein. Moreover, the effects of Bordetella adenylate cyclase toxin on granulosa cell steroidogenesis were functionally integrated with other regulatory responses, since the non-cAMP dependent effector, estradiol 17-beta, interacted synergistically with bacterial adenylate cyclase in stimulating progesterone production. We conclude that exogenous adenylate cyclase isolated from B. pertussis can be functionally integrated into the cAMP-dependent effector pathway of granulosa cells with a resulting increase in intracellular cAMP concentrations, augmented biosynthesis of progesterone and pregnenolone, enhanced synthesis of immunospecific cytochrome P-450scc and adrenodoxin, and synergistic interactions with a non-cAMP-dependent ovarian effector hormone (estradiol).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗

PubMed1988

Immunoblot analysis of cholesterol side-chain cleavage cytochrome P-450 and adrenodoxin in corpora lutea of cyclic and late-pregnant sheep.

The specific contents of cytochrome P-450scc and adrenodoxin in corpora lutea of late pregnant sheep were, respectively, 1/5 and 1/8 that of corpora lutea of the oestrous cycle, suggesting lower steroidogenic enzyme capacity in the former. The contents of Complex V proteins were also lower in the corpora lutea of late pregnancy. It was observed in the immunoblots of both Complex V and cytochrome P-450scc that immunoreactive bands of molecular weights lower than the native proteins were present in the samples from corpora lutea of late pregnancy, indicative of degradation of the native enzymes. It is concluded that corpora lutea of sheep during late pregnancy have a much lower enzyme capacity for steroidogenesis than do those of the oestrous cycle (mid-luteal phase) due to a reduction in the content of cytochrome P-450scc and adrenodoxin. The reduction in the levels of steroidogenic enzyme proteins appears to be unspecific and probably reflects an overall demise in mitochondrial functions.

Adrenodoxin↗

PubMed1988

Secretion of progesterone and prostaglandins by cells of bovine corpora lutea from three stages of the luteal phase.

The secretion of prostaglandins (PGs) by bovine corpora lutea was investigated. Corpora lutea from the early, early-mid and late-mid stages of the luteal phase were dissociated by collagenase treatment and cultured in monolayer in Dulbecco's modified Eagle's medium containing 10% (v/v) fetal calf serum. Treatment with either LH (100 ng/ml) or dibutyryl cyclic AMP (dbcAMP; 1 mmol/l) had no effect on progesterone secretion by early luteal phase cells but stimulated progesterone secretion two- to fourfold by cells from the latter stages. The secretion rates, per microgram cell protein, of 6-keto-PGF1 alpha, PGE2 and PGF2 alpha were substantially greater in cells from the early luteal phase than in those from the latter stages, however, all changes in PG secretion in response to treatments were qualitatively similar between cells from the three stages of the luteal phase. The secretion rate of 6-keto-PGF1 alpha was greater than that of PGE2 or PGF2 alpha and was inhibited by treatment with indomethacin (28 mumol/l) but unaltered by treatment with LH, dbcAMP or butyrate (1 mmol/l). Secretion of PGE2 was inhibited by indomethacin but stimulated two- to threefold by treatment with either dbcAMP or butyrate. Secretion of PGF2 alpha was minimal and not inhibited further by treatment with indomethacin, but was stimulated 10- to 40-fold with dbcAMP. Indomethacin treatment inhibited the stimulatory effect of dbcAMP; butyrate had no effect on PGF2 alpha secretion. Treatment with LH had no effect on any of the PGs measured. In these experiments the secretion of progesterone appeared unrelated to any changes in the secretion of PGs.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Adaptive pain inhibition in murine resident-intruder interactions.

In dyadic encounters with aggressive resident conspecifics, male intruder mice display an initial acute nonopioid analgesia followed by a more enduring opioid analgesia. The former reaction occurs in association with active defense (flight or fight) and can be seen in response to the scent of an aggressive conspecific or defeat experience per se. In contrast, the latter (opioid) reaction is associated with passive defense (immobility) and occurs in response to extended conspecific attack. The mechanisms underlying these two ecologically-relevant forms of pain inhibition are contrasted and the phenomena are discussed in relation to the question of adaptive significance.

Adaptation, Physiological↗

PubMed1987

Mechanisms subserving the steroidogenic synergism between follicle-stimulating hormone and insulin-like growth factor I (somatomedin C). Alterations in cellular sterol metabolism in swine granulosa cells.

Swine granulosa cells respond to follicle-stimulating hormone (FSH) and the insulin-like growth factor, IGF-I (somatomedin C), with synergistic increases in progesterone production. This facilitative interaction was not attributable to decreased catabolism of progesterone to 20 alpha-hydroxypregn-4-en-3-one, but rather to enhanced pregnenolone biosynthesis observed in response to provision of 25-hydroxycholesterol as exogenous sterol substrate. The latter evidence of increased functional cholesterol side-chain cleavage activity was accompanied by augmented incorporation of [35S]methionine into specific immunoisolated components of the cholesterol side-chain cleavage apparatus, viz. cytochrome P-450scc and adrenodoxin. The synergism between FSH and IGF-I could be sustained over 4 days of serum-free monolayer culture. Under these conditions, compactin, a competitive inhibitor of de novo endogenous cholesterol biosynthesis, suppressed stimulated progesterone production by approximately equal to 50%. However, synergism was not expressed at the levels of [14C]acetate incorporation into nonsaponifiable lipids or endogenous 3-hydroxy-3-methylglutaryl coenzyme A reductase activity per se. Conversely, exogenous sterol substrate provided in the form of low-density lipoprotein (LDL)-borne cholesterol increased the absolute magnitude of the combined actions of IGF-I and FSH by 3-6-fold. This increase in steroidogenesis in response to LDL was associated with enhanced surface binding, internalization, and degradation of [125I] iodo-LDL. In addition, when granulosa cells were incubated with [3H]cholesteryl linoleate-labeled LDL, FSH and IGF-I synergistically augmented the intracellular accumulation of [3H]cholesterol and [3H]cholesteryl ester and the production of [3H]progesterone. Moreover, FSH and IGF-I coordinately increased the total mass of free and esterified cholesterol contained in granulosa cells. We conclude that FSH and IGF-I can augment absolute rates of progestin biosynthesis by granulosa cells by activating dual mechanisms: stimulation of functional cholesterol side chain cleavage activity and enhancement of effective cellular uptake and utilization of low-density lipoprotein-borne sterol substrate.

Animals↗

PubMed1987

Benzodiazepine ligands, nociception and 'defeat' analgesia in male mice.

Recent studies have indicated that defeat experience induces acute non-opioid analgesia in intruder mice. To investigate the potential involvement of benzodiazepine receptors in this biologically-relevant form of environmentally-induced antinociception, we initially assessed the effects of some benzodiazepine ligands on basal nociception (tail-flick assay). Chlordiazepoxide (5-30 mg/kg), midazolam (0.625-5 mg/kg), diazepam (0.5-4 mg/kg), Ro15-1788 (5-80 mg/kg) and CGS8216 (5 mg/kg) were found to be ineffective in altering basal nociception. However, higher doses of CGS8216 (10-20 mg/kg) induced significant analgesia, an effect also observed with the beta-carboline derivatives FG7142 (5-20 mg/kg) and DMCM (1-2 mg/kg). Time-course analyses revealed that the onset of CGS8216 analgesia was slower than for FG7142 and DMCM, but that all three drugs produced long-lasting elevations in tail-flick latencies. The analgesic effects of FG7142 and DMCM were completely reversed by Ro15-1788 (20 mg/kg) and by chlordiazepoxide (20 mg/kg), suggesting mediation by benzodiazepine receptor mechanisms. Although CGS8216 analgesia was also reversed by Ro15-1788, it was unaffected by chlordiazepoxide; however, diazepam (5 mg/kg) did significantly attenuate the reaction. Further studies indicated that the antinociceptive consequences of defeat experience were dose-dependently blocked by Ro15-1788 (10-40 mg/kg) and by diazepam (0.5-2 mg/kg). Surprisingly, however, neither chlordiazepoxide (5-20 mg/kg) nor midazolam (1.25-2.5 mg/kg) blocked "defeat" analgesia under present test conditions. Although several issues remain unresolved, present findings would not be inconsistent with the proposal that stimuli associated with the acute stress of defeat experience release an endogenous ligand which acts in an "inverse agonist-like" manner at benzodiazepine sites.

Analgesia↗

PubMed1987

Regulation of the biosynthesis of steroidogenic enzymes.

Recombinant DNA technology can permit study of the regulation of steroid hydroxylase gene expression at three levels. The first of these is cAMP-regulated gene expression. In the adrenal, ACTH, via cAMP, increases the expression of the genes for all of the cytochrome P-450 species involved in the steroid biosynthetic pathway, as well as the iron-sulfur protein, adrenodoxin. This action of cAMP is inhibited by cycloheximide, suggestive of the involvement of a regulatory protein factor in mediating this action of cAMP. The second level is tissue-specific regulation of steroid hydroxylase gene expression. An example of this which we have studied is the expression of cholesterol side-chain cleavage cytochrome P-450 (P-450sec) and 17 alpha-hydroxylase cytochrome P-450 (P-450(17) alpha) in the bovine ovary. P-450sec is expressed at high levels in the corpus luteum but at low levels in follicles, whereas P-450(17)alpha is expressed in follicles, but is undetectable in the corpus luteum. The third level is fetal imprinting. A number of the cytochrome P-450 species involving in the steroidogenic pathway are expressed in the fetal adrenal at a time when exposure of the gland to ACTH is very low, suggestive that factor(s) other than pituitary ACTH mediate this expression in fetal life.

Adrenal Glands↗

PubMed1987

Are the analgesic effects of social defeat mediated by benzodiazepine receptors?

Social conflict in mice is associated with at least two forms of analgesia. A long-lasting opioid reaction is evident in intruder mice exposed to prolonged attack, whilst an acute non-opioid analgesia is seen in response to either defeat experience per se or the territorial scent-marking of an aggressive conspecific. Recent work from this laboratory has suggested that the non-opioid analgesic reaction to defeat experience may be mediated via benzodiazepine receptor mechanisms. The present studies were designed to further test this tentative hypothesis. Results confirmed that defeat analgesia is dose-dependently blocked by Ro15-1788 (20-40 mg/kg) and diazepam (2-4 mg/kg), and also indicated partial antagonism of the reaction by CGS8216 (2.5 mg/kg). The partial agonists CGS9896 (2.5-20 mg/kg) and ZK91296 (2.5-20 mg/kg) were ineffective in blocking the reaction, a finding also obtained with the full agonist ZK93423 (0.05-10 mg/kg). However, the antagonist/weak inverse agonist ZK93426 was found to possess significant intrinsic analgesic activity (10 mg/kg) and to enhance defeat analgesia (5-10 mg/kg). Although several interpretative frameworks for the current pharmacological profile are considered, it is concluded that full clarification of the substrates of defeat analgesia must await further investigations.

Analgesia↗

PubMed1987

Social conflict analgesia: inhibition of early non-opioid component by diazepam or flumazepil fails to affect appearance of late opioid component.

Two forms of analgesia (opioid and non-opioid) are associated with social conflict in mice. The non-opioid form is seen in response to the scent of an aggressive conspecific or defeat experience, whilst the opioid form occurs in response to extended conspecific attack. Recently, it has been reported that the non-opioid reaction is dose-dependently blocked by diazepam and by Flumazepil (Ro15-1788; a benzodiazepine receptor antagonist). In view of the temporal relationship between these two reactions, the present study was conducted to determine whether activation of non-opioid substrates is a necessary precursor to the development of opioid analgesia. Results indicate that inhibition of non-opioid analgesia by diazepam (2-4 mg/kg), or by Flumazepil (20-40 mg/kg), does not alter the opioid analgesic reaction to conspecific attack. Findings are discussed in relation to the presumed adaptive significance of these biologically-meaningful forms of pain inhibition.

Aggression↗

PubMed1987

Changes in content of cytochrome P450(17)alpha, cytochrome P450scc, and 3-hydroxy-3-methylglutaryl CoA reductase in developing rat ovarian follicles and corpora lutea: correlation with theca cell steroidogenesis.

The following study was undertaken to determine which hormones (luteinizing hormone, LH, and prolactin, PRL) and enzymes (cytochrome P450(17)alpha, nicotinamide adenine dinucleotide phosphate [NADPH]-cytochrome P450 reductase, 3-hydroxy-3-methylglutaryl [HMG] CoA reductase, cholesterol side-chain cleavage cytochrome P450 [P450scc], and adrenodoxin) were associated with the regulation of androgen biosynthesis by developing rat follicles and corpora lutea in vivo as well as by thecal explants maintained in culture. Immunoblots of soluble cell extracts of small antral (SA), preovulatory (PO), and luteinizing (PO + human chorionic gonadotropin [hCG], 7 h) follicles, newly formed corpora lutea (PO + hCG, 24 h), and corpora luteal isolated on Day 15 of pregnancy, demonstrated that cytochrome P450(17)alpha was low in SA follicles, selectively increased 4-fold in PO follicles, and decreased to less than 10% within 7 h after hCG. Filter hybridization assays using a 32P-labeled cytochrome P450(17)alpha cDNA probe demonstrated that changes in the content of P450(17)alpha mRNA exhibited a pattern similar to that of the enzyme. Conversely, immunoblots for other microsomal enzymes either exhibited no change (NADPH cytochrome P450 reductase) or a transient increase after the hCG surge (HMG CoA reductase), whereas the mitochondrial enzymes either increased markedly in association with luteinization (cytochrome P450scc) or were increased in a more transient manner (adrenodoxin). The LH-induced loss of cytochrome P450(17)alpha in vivo was not associated with loss of androgen biosynthesis when luteinizing theca were placed in culture in medium containing either LH or LH and PRL, suggesting that other hormones, or the presence of other cell types, are required to maintain the decrease in cytochrome P450(17)alpha in vivo. Conversely, the LH-induced increase in cytochrome P450scc in vivo was associated with the maintenance of elevated progesterone production by theca in culture, suggesting that cytochrome P450scc may be constitutively expressed in luteinized theca. Thus, thecal cell cytochrome P450(17)alpha and the regulation of its content and mRNA by LH are pivotal to the biosynthesis of androgens, the obligatory precursors for estradiol biosynthesis and the consequent development of preovulatory follicles. The molecular basis for the different effects of low versus elevated concentrations of LH on cytochrome P450(17)alpha, as well as cytochrome P450scc, remain to be determined.

Animals↗