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Biomedical subjects

F Kamel

Publications and source records attributed to F Kamel.

At least 37 records · Page 2Linked to original sources
PubMed1990

Altered regulation of pituitary gonadotropin-releasing hormone (GnRH) receptor number and pituitary responsiveness to GnRH in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases the potency of androgens as feedback inhibitors of luteinizing hormone (LH) secretion. Our objectives were to determine if this increase is due to pituitary or hypothalamic dysfunction (or both), and to investigate the mechanism by which TCDD produces this effect. Seven days after dosing, TCDD inhibited the compensatory increases in (i) pituitary gonadotropin-releasing hormone (GnRH) receptor number, (ii) LH secretory responsiveness of the pituitary to GnRH, and (iii) plasma LH concentrations which should have occurred in response to TCDD-induced decreases in plasma testosterone concentrations. TCDD did not inhibit these compensatory responses in the absence of testicular hormones, while treatment of castrated rats with testosterone restored the ability of TCDD to prevent these increases. These findings demonstrate that TCDD alters the androgenic regulation of pituitary GnRH receptor number and pituitary responsiveness to GnRH stimulation. The pituitary is therefore a target organ for TCDD; whether a hypothalamic defect is also involved in the altered regulation of LH secretion was not resolved. The compensatory increases in pituitary GnRH receptor number and plasma LH concentration elicited by low plasma testosterone concentrations were inhibited by similar doses of TCDD (ED50 20 micrograms TCDD/kg for both responses). We concluded that TCDD increases the potency of androgens as feedback inhibitors of LH secretion by increasing their potency as regulators of both pituitary GnRH receptor number and GnRH responsiveness. This is the first demonstration that TCDD treatment (i) affects pituitary responsiveness to a hormone secreted by a peripheral organ (testosterone), and (ii) alters the regulation of pituitary responsiveness to a hypothalamic hormone (GnRH).

Androgens↗
PubMed1990

Increase in luteinizing hormone content occurs in cultured human fetal pituitary cells exposed to gonadotropin-releasing hormone.

To investigate the mechanisms by which GnRH regulates LH production during intrauterine life, dispersed pituitary cells from second trimester human fetuses were cultured on extracellular matrix-coated plates for 48 h. Exposure of cells to 3 x 10(-10) mol/L GnRH for 1-48 h significantly increased cumulative LH secretion compared to that in respective controls (P less than 0.01). The rate of GnRH-stimulated LH release was accelerated during the first 6 h, after which it declined to a level similar to that of basal release. This phenomenon was associated with a decrease in the GnRH concentration of the medium. Exposure of cells to GnRH (3 x 10(-10) to 10(-6) mol/L) for 48 h induced a dose-dependent elevation of total LH which correlated with an increase in releasable, but not cellular, LH. Desensitization to GnRH (10(-7) mol/L) occurred when cells were cultured with pharmacological amounts of GnRH for 48 h. These results indicate that GnRH induces the increase in total and releasable LH in human fetal pituitary cells. These cells also appear to inactivate GnRH. Thus, GnRH may increase LH production in the human fetal pituitary and the pituitary receptor mechanism may be involved in GnRH action on LH release during intrauterine life.

Cells, Cultured↗
PubMed1989

Estrogenic effects of phenol red on rat pituitary cell responsiveness to gonadotropin-releasing hormone.

This study investigated whether phenolsulfonphthalein (PR), a common pH indicator in tissue culture media, affects luteinizing hormone (LH) secretion from rat pituitary cells or 17 beta-estradiol (E2) augmentation of pituitary responsiveness to gonadotropin-releasing hormone (GnRH). PR enhanced GnRH-stimulated LH secretion and shifted the GnRH dose-response curve leftward with a relative potency ratio of 0.24 +/- 0.09 (+/- SE; p less than 0.01). The effect of E2 on LH release was significantly diminished by PR, which elevated GnRH-stimulated LH secretion in the absence of E2. This phenomenon was elicited by PR from different sources and was inhibited by the antiestrogen Cl628. Thus, PR exerted estrogen-like effects on rat pituitary cells and caused an underestimation of the degree to which E2 enhanced GnRH-stimulated LH secretion.

Animals↗
PubMed1988

Gonadal steroid effects on LH response to arachidonic acid and protein kinase C.

Cultured rat pituitary cells were used to examine, first, the effects of luteinizing hormone-releasing hormone, Ca2+ mobilization, protein kinase C (PKC) activation, and arachidonic acid (AA) on luteinizing hormone (LH) secretion and AA release, and, second, gonadal steroid modulation of these effects. A23187, 12-O-tetradecanoylphorbol 13-acetate (TPA), and AA stimulated LH secretion by both perifused and static cultures; TPA facilitated the responses to both A23187 and AA. LHRH, A23187, and TPA stimulated AA release. Inhibition of AA metabolism reduced the LH responses to LHRH, A23187, TPA, and melittin. Pretreatment with testosterone inhibited the LH response to LHRH but not the responses to TPA or AA. Pretreatment with 17 beta-estradiol stimulated the LH responses to LHRH, TPA, and low concentrations of AA. These results suggest that LHRH action involves a cascade of events, in which the effects of Ca2+ mobilization and PKC activation are mediated at least in part by AA release. They further suggest that both testosterone and 17 beta-estradiol modulate LH secretion by affecting AA release; 17 beta-estradiol may also affect some process subsequent to AA release.

Animals↗
PubMed1987

Effects of luteinizing hormone (LH)-releasing hormone pulse amplitude and frequency on LH secretion by perifused rat anterior pituitary cells.

Recent studies have shown that LH secretion in vivo is pulsatile. In the present study, a cell perifusion system was employed to characterize the pituitary response to changes in LHRH pulse amplitude and frequency. Increases in pulse amplitude consistently elevated both mean LH levels and the amount of LH released in response to individual LHRH pulses. The EC50 for LHRH was approximately 3 nM. Increases in pulse frequency also increased mean LH levels, but frequencies of three or more pulses per h were associated with a decrease in the amount of LH released per pulse. Alterations in LHRH pulse characteristics changed qualitative as well as quantitative aspects of LH secretion, with high frequency, high amplitude pulses producing a biphasic response to LHRH. Initially a self-priming response was seen during the second and third hours of stimulation; this was followed by increasing desensitization of the cultures to LHRH. These results, by defining the pituitary response to specific conditions of stimulation, will help to clarify the relationship of LHRH stimulation to LH secretion in vivo.

Animals↗
PubMed1987

Gonadal steroids modulate pulsatile luteinizing hormone secretion by perifused rat anterior pituitary cells.

Recent studies have shown that LH secretion is pulsatile and that LH pulse characteristics are affected by the prevailing steroid environment in both male and female rats. In the present study, a cell perifusion system was used to examine the effects of testosterone (T) and 17 beta-estradiol (E) on LHRH-stimulated pulsatile LH secretion. T inhibited LH secretion, increasing the EC50 for LHRH, while E stimulated secretion, lowering the EC50. Steroid effects were independent of both LHRH pulse amplitude and frequency. E also affected the pattern of LH secretion by facilitating both LHRH self-priming and desensitization to LHRH. These results show that steroids can affect pulsatile LH secretion by actions exerted at the pituitary level and that steroids can induce both quantitative and qualitative changes in LH secretion in the presence of an invariant LHRH stimulus. These results help to elucidate the mechanisms underlying steroid feedback in vivo, since reduction in pituitary responsiveness to LHRH may play an important role in T feedback, while facilitation by E of both self-priming and desensitization may serve to increase the magnitude and shorten the duration of the proestrous LH surge.

Animals↗
PubMed1987

Modulation of gonadotropin secretion by corticosterone: interaction with gonadal steroids and mechanism of action.

The effects of corticosterone (B) on pituitary responsiveness to LHRH and on gonadal steroid modulation of gonadotropin secretion were investigated using primary cultures of rat pituitary cells. Cultures were treated for 2 days with steroids and then challenged with LHRH for 4 h. B inhibited LH secretion, increasing the EC50 for LHRH from 1.40 to 4.96 nM. The reduction in LH release was accompanied by an increase in cell LH, so that the total amount of LH present in the cultures was unchanged. The EC50 for the effect of B on LH secretion was 0.57 microM. B increased the total amount of FSH present in the cultures. At high concentrations of B (10-100 microM), this effect was associated with an increase in FSH secretion. Testosterone inhibited LH secretion in both the absence and the presence of B. B had no effect in the presence of maximal concentrations of testosterone but augmented the inhibitory effect of lower concentrations. Estradiol (E) stimulated LH secretion in both the absence and the presence of B. However, the stimulatory effect of E was reduced by B, so that cultures treated with both B and E secreted no more LH than untreated cultures. B inhibited the LH secretory responses to Ca2+ influx and protein kinase C activation but did not affect the response to arachidonic acid, suggesting that the mechanism of B action may involve an inhibition of arachidonic acid release. Together these results indicate that the inhibitory effects of stress on reproduction are mediated at least partially by the inhibitory effects of B on LH secretion.

Animals↗
PubMed1985

A detailed examination of the in vivo and in vitro effects of ACTH on gonadotropin secretion in the adult rat.

These studies were designed to: (1) determine the effects of continuous infusion of synthetic ACTH(1-24) on postcastration changes in serum and pituitary LH, FSH and prolactin in the male rat; (2) assess the effects of adrenalectomy on the gonadotropin and prolactin response to ACTH, and (3) test the hypothesis that ACTH may directly (not via adrenal factors) alter gonadotropin secretion at the brain and/or pituitary level. Adult male rats were either orchidectomized (ORX) or orchidectomized-adrenalectomized (ORX-ADX), and were treated continuously for 6 days with ACTH(1-24) (10 micrograms/day) or saline using an osmotic minipump. Animals were killed on day 6 following castration. ACTH treatment reduced serum LH and prolactin levels in ORX rats to mean values +/- SE of 204 +/- 25 and 37 +/- 3 ng/ml respectively, compared to 366 +/- 72 and 62 +/- 7 ng/ml in saline-treated ORX animals. Serum FSH concentrations were not altered by ACTH administration. Pituitary concentrations of LH and FSH, but not prolactin were enhanced by ACTH treatment. Adrenalectomy had no effect on serum and pituitary gonadotropin and prolactin levels, but abolished the effects of ACTH on these parameters. Central (intracerebroventricular) infusion of ACTH(1-24) (6 micrograms/day X 4 days) failed to alter the rise in serum LH in male rats following orchidectomy. Acute treatment with large doses of ACTH of perifused anterior pituitary glands from male rats and chronic treatment with ACTH of enzymatically dispersed anterior pituitary cells from female rats did not influence basal or GnRH-stimulated LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1984

[Epidemiology of drug abuse in the French army].

French medical service has carried on an epidemiological study of toxicological conducts for the last ten years. But, in 1982, the number of registered cases has undergone a deflation of 19 p. 100 compared en 1981. Without to jump to conclusions, then, general statistics note an aggravation of these toxicological conducts, such an acknowledgment is hopeful. It would be a sign of nearest decline of endemic toxicomania in our state.

France↗
PubMed1983

Aromatization: important for testosterone's developmental influences on the neurocircuits mediating cervically stimulated prolactin secretion in the female rat.

Adult female rats treated neonatally with testosterone or estrogen fail to respond to cervical stimulation with episodic prolactin release. The developmental action of testosterone is inhibited by co-administration of 1,4,6-androstatriene-3,17-dione at a dose sufficient to inhibit the testosterone-induced rise in estrogen receptors in limbic brain cell nuclei. These data suggest the importance of aromatization for testosterone action.

Animals↗
PubMed1983

Gonadal steroid modulation of LH secretion stimulated by LHRH, Ca2+ and cAMP.

Primary cultures of enzymatically dispersed rat pituitary cells were used to examine steroid effects on LH secretion stimulated by LHRH, Ca2+ and cAMP. Cultures were pretreated for 48 h with testosterone (T) or 17 beta-estradiol (E) and then challenged for 4 h with various secretogogues. T did not affect basal LH secretion; it inhibited the responses to Ca2+ and LHRH; and it potentiated the response to cAMP. E stimulated both basal LH secretion and the responses to all secretogogues, without affecting cell LH content. Thus, T affects stimulus-secretion coupling, while E affects secretion per se. All steroid effects were blocked by steroid antagonists, indicating that steroid action is receptor-mediated regardless of the secretogogue involved. The similarity of steroid effects on the responses to LHRH and Ca2+ but not cAMP suggests that Ca2+ rather than cAMP is a second messenger for LHRH, and that steroid action occurs at some step subsequent to LHRH-stimulated Ca2+ mobilization.

Animals↗
PubMed1983

Behavioral and neuroendocrine effects of long-term progesterone treatment in the rat.

Progesterone and estradiol, alone or in combination, were administered to ovariectomized rats for 2 weeks. Progesterone alone had no effect on body weight, luteinizing hormone (LH) secretion, receptivity or brain cytoplasmic progestin receptors (CPR). Progesterone in combination with estradiol significantly attenuated estrogen suppression of weight gain and estrogen stimulation of receptivity, the LH afternoon surge and induction of CPR, but did not affect the negative feedback of estrogen on morning LH levels. The decrease in CPR after 2 weeks of progesterone is very similar in magnitude to the decrease observed following acute treatment, suggesting that, unlike neurotransmitter agonists and glucocorticoids, progesterone does not cause down regulation of its receptors in the brain following chronic treatment.

Animals↗
PubMed1982

Gonadal steroid modulation of LHRH-stimulated LH secretion by pituitary cell cultures.

Enzymatically dispersed rat pituitary cells were grown in primary culture, and LHRH-stimulated LH secretion was measured. Testosterone (T) decreased and 17 beta-estradiol (E) increased pituitary responsiveness to LHRH. The effect of E on LH secretion was partly due to an increase in LH content. There was a latent period of 12 h for E and 18 h for T between the onset of steroid treatment and the manifestation of steroid action. Neither steroid was required to be continuously present in order to exert its effects. After steroid withdrawal, the effect of T persisted for 72 h and that of E for more than 96 h. The actions of both steroids were blocked by protein-synthesis inhibitors. These results are consistent with the hypothesis that steroid effects rely on a mechanism involving alterations in protein synthesis; the affected proteins may be involved in the process of LHRH action.

Animals↗
PubMed1978

The effect of medial preoptic area lesions on sexually stimulated hormone release in the male rat.

Male rats were subjected to bilateral electrolytic lesions in the medial preoptic area (mPOA). These lesions disrupted sexual behavior without affecting basal levels of luteinizing hormone (LH), prolactin (PRL), or testosterone (T). During exposure to an estrous female, intact and sham-operated rats mated; these rats showed elevations in LH, PRL, and T levels. Lesioned rats, which did not mate, showed elevations in LH but not PRL or T levels. These results demonstrate that the mPOA is not required for sexually stimulated LH release. The failure of lesioned rats to release PRL and T may be secondary to their failure to mate. Alternatively, the mPOA may participate in sexually stimulated PRL release, while T release may depend on prior elevations in both LH and PRL levels. LH release may be related to arousal, and PRL release to consummation, providing a hormonal analogy for the dual mechanism theory of sexual behavior.

Animals↗