Shariful Islam Naik
@buruniv.ac.in
Bachelor of Engineering in Electrical Engineering
University Institute of Technology, The University of Burdwan
Shariful Islam, Commonly Known as Shariful Islam Naik is an Engineer & Preacher. Who is Best Known for Being the Founder & Chairman of Peace TV Foundation & CEO of Peace TV.
EDUCATION
Bachelor of Engineering (BE) in University Institute of Technology, The University of Burdwan
RESEARCH INTERESTS
Comparative Religion, Qur'an, Hadith, Electrical Engineering, Power Station, Power Engineering
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Umair Mahmood, Muhammad Imran, Salma Iqbal Naik, Huma Arshad Cheema, Anjum Saeed, Muhammad Arshad, and Saqib Mahmood
Elsevier BV
Type I galactosemia is an inborn error resulting from mutations on both alleles of the GALT gene, which leads to the absence or deficiency of galactose-1-phosphate uridyltranseferase (GALT), the second of three enzymes catalyzing the conversion of galactose into glucose. On the basis of residual GALT activity, Type I galactosemia is classified into severe "Classical" and mild "Duarte" phenotypes. Classical galactosemia is frequently associated with S135L, Q188R and K285N mutations in the GALT gene. The functionally neutral N314D variation in the GALT gene is associated with Duarte galactosemia and is widespread among various worldwide populations. The present study aimed at detecting S135L, Q188R and K285N mutations and the N314D variant in the GALT gene by PCR using amplification refractory mutation system (ARMS). ARMS assays were established using standard DNA samples and were used for 8 galactosemia patients and 190 unrelated normal subjects all of Pakistani origin. S135L and K285N mutations were present neither in galactosemia patients nor in normal subjects. Only one galactosemia patient carried Q188R mutation that was in homozygous state. However, the N314D variant was frequently found both in affected (7 out of 16 alleles) and normal subjects (55 out of 380 alleles). This finding indicates that Duarte allele D314 might be far more common in Pakistani population than in European and North American ones.
Frank W.J. Anderson, Sujata I. Naik, Shingairai A. Feresu, Bette Gebrian, Manju Karki, and Sioban D. Harlow
Wiley
To determine the incidence of perceived pregnancy complications and associated factors.
Frank W. J. Anderson, Sarah U. Morton, Sujata Naik, and Bette Gebrian
Springer Science and Business Media LLC
AbstractObjective: To determine the odds of death of children when a woman of reproductive age dies from maternal or non maternal causes in rural Haiti.
Methods: Deaths among reproductive aged women between 1997 and 1999 in and around Jeremie, Haiti were classified as maternal or non maternal and matched to female, non-deceasesd controls based on village, age, and parity. Information regarding the health and survival of all of the offspring under 12 years old of the identified women was extracted from the Haitian Health Foundation (HHF) Health Information System (HIS). Additional demographic information was obtained through interviews with the mothers for controls and with family members for cases. Two analyses on child death were conducted; 1) the odds of death for each individual child after a mother’s death and 2) the odds of one of the children in a family dying after the mother’s death.
Findings: If a family experiences a maternal death, that family has a 55.0% increased odds of experiencing the loss of a child less than 12, whereas when a non maternal death occurs, no increased odds exists. When children of cases were compared to children of controls, mean weight z-scores were the same for the periods corresponding to before and after the maternal deaths. After a maternal death, dosage of BCG (Bacillus Calmette-Guerin) TB (tuberculosis) immunization for the surviving child is significantly lower, as are dosage of measles immunization and the first dose of vitamin A.
Conclusions: This study shows that a maternal death significantly effects the survival of children in a family in a greater way than a non maternal death.
S.D. Abbot, S.I. Naik, and R.N. Clayton
Elsevier BV
Experiments were performed to study gonadotroph responsiveness to gonadotrophin releasing hormone (GnRH) in vitro in dispersed pituitary cells from ovariectomised rats and mice when GnRH binding sites were increased or reduced, respectively. Maximal/basal LH release after GnRH treatment of intact female rat pituitary cells was 4.7 to 9.7-fold (range n = 3 expts.) compared to 3.4 to 5.0-fold for cells from ovariectomised rat donors. Both basal and maximal GnRH-stimulated LH release from ovariectomised (OVX) rat pituitary cells were 1.5 to 3-fold greater than from intact rat cells, which corresponded to increased LH content of the cells. There was no significant change in the GnRH ED50 concentration (intact = 2.3 +/- 0.03 X 10(-10) M; OVX = 3.3 +/- 0.08 X 10(-10) M (mean +/- SEM, n = 3 expts.)), despite a 57-88% increase in GnRH binding sites in ovariectomised rat pituitary cells. Basal and maximal LH release from ovariectomised mouse pituitary cells was 1.5 to 3-fold greater than that from intact mouse pituitary cells. There was no change in the GnRH ED50 concentration (intact = 4.3 +/- 2.3 X 10(-9) M; OVX = 3.4 +/- 0.9 X 10(-9) M (mean +/- SEM, n = 3 expts.)), even though GnRH binding sites were reduced by 40-73% in the cells from ovariectomised mice. These data indicate that changes in GnRH binding sites of the magnitude observed after ovariectomy play no part in the regulation of gonadotroph responsiveness to GnRH, which is determined by changes in post-receptor events, one of which is an increase in cellular LH.
R.N. Clayton, A. Detta, S.I. Naik, L.S. Young, and H.M. Charlton
Elsevier BV
The relationship between pituitary GnRH receptors (GnRH-R) and LH responsiveness to GnRH stimulation is not straightforward. In some circumstances, e.g. post-gonadectomy of rats, in lactating rats, during the rat, hamster and monkey oestrous cycles there appears to be a good positive correlation between GnRH-R, basal serum LH values and LH responses to exogenous GnRH. However, in mice following gonadectomy GnRH-R fall by 50% while serum LH levels rise by 10-fold, and in cultured pituitary cells, GnRH exposure increases GnRH-R yet desensitizes cellular responsiveness to subsequent GnRH stimulation. Thus, our original hypothesis that GnRH-R regulation was closely coupled to gonadotroph secretory function does not always hold. Further, we and others, using the rat as an experimental model, hypothesised that the pituitary GnRH receptor content reflected the level of previous pituitary exposure to endogenous GnRH. This view is supported with studies in the GnRH deficient hypogonadotrophic hypogonadal (hpg) mouse in which exogenous GnRH rapidly normalises GnRH-R from very low levels, and is accompanied by rapid activation of pituitary FSH synthesis. However, the post-castration fall in GnRH-R in mice, which is opposite to that in rats, does not appear to be so closely related to endogenous GnRH secretion and cannot be reversed by exogenous GnRH. Using the ovariectomised mouse as an experimental model, evidence has been obtained that estradiol, in addition to GnRH, is essential for maintenance of pituitary GnRH-R in this species. Exogenous estradiol stimulates GnRH-R in OVX mice while it reduces the high values in OVX rats. In female mice estradiol and GnRH have additive stimulatory effects on GnRH-R. Thus, there is species variability in the predominant hormonal regulation of GnRH receptors. In rat pituitary cells in vitro up-regulation of GnRH-R can be effected by several agents which stimulate LH release (GnRH, KCl, DbCAMP) as well as some which do not (Ca ionophore at low concentrations). Receptor up-regulation requires Ca2+ mobilisation and protein synthesis. The data obtained from several in vivo and in vitro model systems supports the conclusion that GnRH receptor changes represent another, medium-term, consequence of GnRH action on the gonadotroph and are not always a locus for the modulation of gonadotrophin secretion and synthesis.
S. I. Naik, L. S. Young, G. Saade, A. Kujore, H. M. Charlton, and R. N. Clayton
Bioscientifica
The fall in pituitary GnRH receptors in female mice after ovariectomy (Ovx) was further decreased (greater than 50%), rather than prevented, by treatment with a GnRH antiserum, despite suppression of the post-gonadectomy increase in serum gonadotrophins, suggesting that increased endogenous GnRH secretion is not the mediator of GnRH receptor fall after ovariectomy in mice. Furthermore, GnRH antiserum reduced GnRH receptors by 30-50% in intact normal females, without altering receptor affinity, and rendered serum LH and FSH undetectable but did not reduce receptors in GnRH-deficient, hpg mice. When GnRH was administered to ovariectomized mice this failed to restore receptor values (fmol/pituitary) (intact = 55.3 +/- 2.4; Ovx = 30.1 +/- 2; Ovx + GnRH = 31.6 +/- 2.8), but serum LH was reduced from high post-ovariectomy values (231 +/- 42 ng/ml) to values normal for intact females (24 +/- 2 ng/ml). In contrast, multiple GnRH injections to intact female mice increased GnRH receptor by 35%, while serum LH was reduced to just detectable levels. A marked dissociation between GnRH receptor and serum gonadotrophin concentrations was observed. Administration of oestrogen (E2) plus progesterone (P) to ovariectomized mice in which endogenous GnRH had been immunoneutralized reversed the inhibitory effect of GnRH antiserum on GnRH receptors and increased values above those of ovariectomized controls, although no increase in serum or pituitary gonadotrophin levels was seen in ovariectomized mice treated with E2 + P + GnRH antiserum. Treatment with E2 and P of intact females receiving GnRH antiserum did not prevent the inhibitory effect of antiserum on receptors, while E2 + P treatment alone of intact female mice reduced GnRH receptors by 30%. These data suggest that the gonadal steroids reduce GnRH receptors in intact female mice by inhibiting hypothalamic GnRH secretion, and that a certain degree of pituitary exposure to GnRH is required for maintenance of a normal receptor complement. These results suggest that (1) the fall in GnRH receptors after ovariectomy is primarily attributable to removal of gonadal factors. The fall is not a reflection of alteration in endogenous GnRH interaction with the gonadotroph; (2) homologous ligand 'up-regulation' of GnRH receptors in female mice depends upon the presence of the ovaries; (3) endogenous GnRH is also required for GnRH receptor maintenance in intact female mice; and (4) GnRH receptor and serum gonadotrophin responses to hormonal changes can be dissociated and their relationship is complex.
L. S. Young, S. I. Naik, and R. N. Clayton
Bioscientifica
ABSTRACT Exogenous cyclic adenosine nucleotides increase gonadotrophin-releasing hormone (GnRH) receptors in intact cultured rat pituitary cells in a similar manner to that observed with GnRH itself. In this study the calcium and microtubule dependency of GnRH receptor up-regulation was examined in vitro. Treatment of pituitary cells in Ca2+ and serum-containing media with either GnRH (1 nmol/l), K+ (58 mmol/l) or dibutyryl cyclic AMP (dbcAMP; 1 mmol/l) for 7–10 h routinely resulted in a 50–100% increase in GnRH receptors. Incubation of pituitary cells with the calcium channel blocker verapamil, for 7 h, or the calcium chelator EGTA, for 10 h, had no effect on basal receptor levels but prevented the increase in GnRH receptors stimulated by either GnRH, K+ or dbcAMP. Luteinizing hormone release measured with the same stimulators over a 3-h period was prevented by both verapamil and EGTA. Calcium ionophore (A23187) increased GnRH receptors by 40–60% at low concentrations (10 and 100 nmol/l) while higher concentrations (10 and 100 μmol/l) reduced receptor levels. Luteinizing hormone release was not increased by receptor-stimulating concentrations of A23187, but was by higher concentrations (10 μmol/l). None of these pretreatments, for up to 10 h, impaired the subsequent LH response of the cells to increasing doses of GnRH. Vinblastine (1 μmol/l did not affect basal receptor levels but markedly reduced the increase in GnRH receptors stimulated by GnRH, K+ and dbcAMP. This concentration of vinblastine had no effect on LH release. These results indicate that receptor stimulation by GnRH, K+ and dbcAMP is a calcium-dependent process requiring the integrity of the microtubule system and there is a different calcium requirement for the processes of GnRH receptor up-regulation and LH secretion. J. Endocr. (1985) 107, 49–56
S. I. Naik, G. Saade, A. Detta, and R. N. Clayton
Bioscientifica
ABSTRACT A single injection of gonadotrophin-releasing hormone (GnRH) (60 ng s.c., 42·9 nmol) induced biphasic GnRH receptor regulation in normal intact adult female mice. A transient 22% receptor decrease occurred 30–60 min after injection of GnRH when peak serum decapeptide concentrations were reached (137 ± 41 (s.e.m.) ng/l). This GnRH receptor decrease occurred shortly after the peak serum LH values at 15–30 min. The subsequent rapid (within 1 h) return of GnRH receptor levels to normal suggested transient receptor occupancy by GnRH rather than true receptor loss. At 8 h after injection of GnRH a significant 35% increase in GnRH receptors was consistently observed, when serum GnRH levels were undetectable and serum LH had returned to basal levels. This receptor increase was not due to increased receptor affinity, and was prevented by a non-specific protein synthesis inhibitor. Ovariectomy, which caused a 50% fall in GnRH receptors (59·4 ± 4·9 fmol/pituitary gland in intact controls; 26·9 ± 2·6 in ovariectomized mice) abolished the induction by GnRH of its own receptors, although the initial transient decrease occurred over the period of the acute serum LH and FSH rise. Despite a 50% reduction in GnRH receptors in ovariectomized mice, increased serum gonadotrophin levels and responsiveness to GnRH were maintained, indicating dissociation between receptor changes and gonadotrophin levels. No GnRH receptor up-regulation was observed 8 h after a single GnRH injection (60 ng s.c.) in either intact or orchidectomized normal male mice. However, the same treatment doubled GnRH receptors in GnRH-deficient (hpg) female mice. While GnRH appears to up-regulate its own receptors by a direct action on pituitary gonadotrophs in the GnRH-deficient mouse its action in the normal female mouse pituitary appears secondary to stimulation of a gonadal product, presumably oestrogens. J. Endocr. (1985) 107, 41–47
S. I. Naik, L. S. Young, H. M. Charlton, and R. N. Clayton
Bioscientifica
Treatment of GnRH-deficient (hpg) female mice with oestradiol-17 beta (E2) for 7 days increased GnRH receptors from 4.1 +/- 0.4 fmol/pituitary (control) to 7.2 +/- 0.7 fmol/pituitary (GnRH-treated), and consistently increased pituitary FSH content. Treatment of hpg female mice with E2 plus progesterone (P) for 14 days stimulated GnRH receptors more than did E2 alone, although values still remained lower than those of normal intact female mice. In contrast, GnRH treatment of intact hpg female mice alone, or combined with E2 + P, increased GnRH receptors to values similar to those of intact normal female mice. In contrast, the receptor rise after GnRH treatment alone of ovariectomized hpg mice was significantly less than in intact hpg mice similarly treated. However, the combination of GnRH + E2 + P treatment of ovariectomized hpg mice increased GnRH receptors to normal intact female values, indicating the synergistic actions of these hormones on GnRH receptor up-regulation at the pituitary. Oestradiol treatment of ovariectomized normal female mice prevented the receptor fall after ovariectomy, and when combined with exogenous GnRH further increased receptors to values identical to those of intact female mice receiving GnRH alone. Ovariectomy of hpg mice had no effect on GnRH receptor, serum or pituitary LH and FSH values. There was no change in serum LH concentration after GnRH treatment of hpg female mice, but serum FSH increased and this was accentuated by ovariectomy, indicating that in intact mice an ovarian factor(s) normally inhibits GnRH-stimulated FSH release. This factor did not appear to be an ovarian steroid since serum FSH was not suppressed in intact or ovariectomized GnRH-treated hpg mice concurrently receiving E2 + P treatment. These results suggest that: (1) gonadal steroids alone have a major direct stimulatory action on the pituitary to increase GnRH receptors; (2) the oestrogen-induced increase in GnRH receptors is enhanced in the presence of GnRH; (3) steroids exert inhibitory feedback on gonadotrophin secretion that is mediated at some cellular regulatory locus other than the GnRH-receptor complex.
L.S. Young, S.I. Naik, and R.N. Clayton
Elsevier BV
GnRH, high potassium concentrations, and cAMP derivatives have been previously shown to increase GnRH receptor levels (GnRH-R) in cultured rat pituitary cells. However, the effect of these changes in receptor number on subsequent stimulated LH release has not been investigated. In this study pretreatment of pituitary cells with either 1 nM GnRH, 58 mM KCl, or 1 mM dibutyryl cAMP (dbcAMP) resulted in a 70-100% increase in GnRH-R 7-10 h later. Subsequent LH responses to GnRH in those cells pretreated with GnRH and KCl were markedly reduced and the dose-response characteristics altered such that the curves were non-sigmoidal. When corrected for depletion of cellular LH during the pretreatment period these GnRH response curves were similar to control, implying that hormone depletion was the explanation for apparent desensitisation. By contrast, dbcAMP and low-dose calcium ionophore (0.1 microM A23187) pretreatment, which did not deplete cellular LH, neither enhanced nor decreased subsequent sensitivity to GnRH. Thus, 4 agents which all, under these conditions, increased GnRH receptors did not sensitise gonadotrophs to GnRH. By contrast, pretreatment with 10(-9) and 10(-8) M GnRH for either 12 or 16 h rendered cells completely or partially refractory to further GnRH stimulation, despite an increase in GnRH receptors. This desensitisation could not be explained by cellular LH depletion, and was specific to the homologous ligand since dose-responses to the Ca2+ ionophore A23187 and KCl were normal when corrected for LH depletion. Non-receptor-mediated depletion of cellular LH during A23187 pretreatment (10 microM for 10 h) did not alter subsequent GnRH dose-responses, after correction for LH content. These data indicate that, under these in vitro conditions, the increased GnRH receptors are not functionally linked to the secretory apparatus of the gonadotroph. Furthermore, homologous ligand-induced desensitisation is both time- and concentration-dependent and is mediated largely by post-receptor cellular events independent of cellular LH content. Therefore, post-receptor cellular processes may be more important than changes in GnRH receptors in regulating gonadotrophin secretion. It is suggested that an increase in GnRH receptors may represent a cellular response to generalised gonadotroph activation by a variety of agents, and does not necessarily signify enhanced responsiveness to GnRH.
L. S. YOUNG, S. I. NAIK, and R. N. CLAYTON
The Endocrine Society
In this study the GnRH receptors (GnRH-R) in cultured rat pituitary cells were examined after treatment with GnRH and cyclic nucleotide derivatives. GnRH at doses of between 10(-11) and 10(-8) M caused GnRH-R increases, 10(-9) M resulting in a 50% stimulation of both GnRH-R and LH release. (Bu)2cAMP increased GnRH-R in a dose dependent manner, with a maximal 2-fold increase at 1 mM, with no effect on LH release in serum-containing medium. The time-course of both the GnRH and (Bu)2cAMP stimulation of GnRH-R was similar, with maximal levels being reached between 6-12 h. There was no difference in the GnRH receptor affinity subsequent to either GnRH or (Bu)2cAMP treatment. GnRH-R increases of 70% were observed when pituitary cells were treated with 1 mM cAMP and 8- bromocAMP , but n-butyric acid, adenosine, and cyclic guanosine monophosphate (all 1 mM) were not effective. Fifty eight millimolar KCl resulted in a 2-fold elevation of GnRH-R. Isobutylmethylxanthine (0.2 mM) did not affect basal receptor levels and slightly enhanced the GnRH-and potassium-stimulated increase of GnRH-R, whereas the increase caused by (Bu)2cAMP was completely prevented. Simultaneous treatment of cultured pituitary cells with either GnRH, KCl, or (Bu)2cAMP and cycloheximide completely prevented GnRH-R increases, while not affecting either basal or GnRH and KCl-stimulated LH secretion. None of the cyclic nucleotides stimulated LH release under the culture conditions employed to examine receptor regulation. However, when incubated in medium not containing serum, both (Bu)2cAMP and cyclic guanosine monophosphate stimulated significant LH release. When the pituitary cells were treated with GnRH in medium without serum, no increase in GnRH-R was measured, although LH release was unaffected. However, absence of serum in the medium did not affect either the K+ or (Bu)2cAMP stimulation of GnRH-R. The GnRH antagonist ( DpGlu1 , D-Phe2, D-Trp3,6) GnRH (1 microM) prevented both GnRH- and (Bu)2cAMP-induced increases in GnRH-R, although not that of 58 mM KCl. The antagonist also inhibited GnRH-stimulated LH secretion, although not that caused by KCl.(ABSTRACT TRUNCATED AT 400 WORDS)
S. I. NAIK, L. S. YOUNG, H. M. CHARLTON, and R. N. CLAYTON
The Endocrine Society
The regulation of pituitary GnRH receptors (GnRH-R) by gonadal steroids was examined in female mice housed in a constant environment (six to 8 per cage in same room as males). A 60% decrease in GnRH-R occurred 7 days after ovariectomy (OVX) (9.2 +/- 0.9 fmol/pituitary OVX vs. 25 +/- 2 for intact random estrous cycle controls). The receptor affinity (Ka 1.86 X 10(9) M-1) remained constant in intact and OVX female mouse pituitary particles. The pattern of GnRH-R fall after OVX was similar to that found in male mice, except that the GnRH-R decrease began some 6 h later than in males and serum LH also rose more slowly. Serum FSH was significantly elevated 6 h post OVX. In contrast to males, pituitary LH, in spite of a rapid fall (60%) at 12 h, regained the random, estrous cycle control value by 4 days post OVX and then increased to above this level. Pituitary FSH, unlike in males, remained at the intact value (3.1 +/- 0.24 micrograms/pituitary) up to 24 h post OVX and then gradually rose to 7.9 +/- 0.37 micrograms/pituitary on day 4 and 15.5 +/- 0.32 micrograms/pituitary on day 7. Treatment of OVX female mice with estradiol-17 beta (300 ng/day) attenuated the postcastration GnRH-R fall, and was more effective when combined with progesterone (375 micrograms/day). Progesterone alone was ineffective. The GnRH-R fall post OVX persisted for up to 2 months, despite elevated serum and pituitary LH and FSH levels. GnRH-R fell by 40% in lactating mice (20.6 +/- 0.95-lactating vs. 32.4 +/- 1.25 fmol/pituitary-random, estrous cycling females). Serum LH was reduced by 70% in lactating mice. These findings are qualitatively and quantitatively similar to those in lactating rats suggesting that, in this physiological situation, a similar mechanism may account for the receptor fall in both species. In sex reversed (Sxr) mice (genotypic female-phenotypic male) GnRH-R values were about 50% higher than those of intact normal male and normal, random estrous cycling, female values. This was the only situation in mice in which pituitary GnRH-R increases were observed to date. Serum and pituitary LH and FSH values in Sxr mice were elevated, especially when compared with normal, random estrous cycling female controls. The results indicate that pituitary GnRH-R of female mice fall in response to removal of gonadal steroid feedback, in the same way as males.(ABSTRACT TRUNCATED AT 400 WORDS)
S. I. NAIK, L. S. YOUNG, H. M. CHARLTON, and R. N. CLAYTON
The Endocrine Society
The regulation of pituitary GnRH receptors (GnRH-R) has been examined in male mice (C3H/HeH/101H F1 hybrid) after castration and testosterone replacement. GnRH-R were quantified in individual mouse pituitaries by equilibration with 125I(D-Ser(tBut)6) des Gly10 GnRH N ethylamide and compared with serum and pituitary LH and FSH concentrations. The equilibrium association constant was 2.7 X 10(9) M-1 for both intact and castrated male mouse pituitary GnRH-R. Six hours after orchidectomy there was a transient 50% reduction in GnRH-R; 13.6 +/- 3.8 fmol/pituitary (castrate) vs. 25.4 +/- 2.5 (intact). A subsequent partial return of binding sites began at 12 h, reaching a peak value of 18.2 +/- 1.5 fmol/pituitary (33% increase vs. 6 h) at 24-h post orchidectomy. This was followed by a gradual decrease in GnRH-R, reaching a plateau by 72 h. The decrease in GnRH-R was associated with a rapid (6-12 h) increase in serum LH and serum FSH. The pituitary GnRH-R concentration remained 45% below intact control values for up to 3 months and was accompanied by a persistent 5-fold rise in serum LH values. Treatment of male mice with testosterone propionate (TP), 25 micrograms/day, completely prevented the GnRH-R fall and the serum and pituitary LH responses to castration, whereas 12.5 micrograms/day TP produced variable results and 5 micrograms/day TP were ineffective. In another strain of mouse (BALB/c white). GnRH-R values also fell by 66% at 7 days post orchidectomy, with no change in the receptor affinity. In mice with androgen resistance from birth due to absence of androgen receptors (Tfm mice), GnRH-R were 14.45 +/- 0.49 vs. 19.8 +/- 1.67 fmol/pituitary in normal male littermates, and serum LH was 472 +/- 78 ng/ml compared with 52.5 +/- 11.7 ng/ml in normals. These findings are qualitatively similar to those in orchidectomized normal adult mice. Thus, in contrast to reports in rats, pituitary GnRH-R content falls after orchidectomy in mice. Possible explanations for this consistent finding include: persistent receptor occupancy by increased endogenous GnRH secretion, endogenous GnRH-induced receptor loss (down-regulation), or a species difference in the pituitary GnRH-R response to removal of negative steroid feedback, unrelated to changes in endogenous GnRH secretion.
A. Detta, S.I. Naik, H.M. Charlton, L.S. Young, and R.N. Clayton
Elsevier BV
This study demonstrates that a single subcutaneous injection of gonadotrophin-releasing hormone (GnRH) (60 ng) to GnRH-deficient (hpg) male mice causes a doubling of pituitary GnRH receptors (GnRH-R). No change in GnRH-R occurs during the time of LH release (15-60 min) or up until 4 h post-GnRH. Between 4 and 12 h there is a progressive increase in GnRH-R, which is still apparent 24 h later. No induction of GnRH-R occurs after the same treatment of intact adult normal mice. The same degree of GnRH-R induction occurs 12 h after a single GnRH injection (60 ng) to orchidectomized hpg male mice, indicating that this effect is mediated by a direct action of GnRH on the pituitary gonadotroph, rather than being secondary to stimulation of some gonadal product. Homologous ligand GnRH-R induction in hpg mouse pituitaries in vivo is prevented by prior treatment with cycloheximide, a non-specific protein synthesis inhibitor. Cycloheximide alone had no effect on GnRH-R in normal male mice but when combined with GnRH caused a 40% depletion of receptors, implying ligand-induced receptor loss without subsequent replenishment. The similarity between the extent, time-course, and dependence on protein synthesis of GnRH induction of its own receptors in vivo and in cultured pituitary cells in vitro indicates that the hpg mouse pituitary behaves like an in vivo pituitary cell culture system in this respect. Similarity of data derived from this in vivo model provides direct support for the view that in vitro studies on the cellular mechanism of GnRH action can be physiologically relevant to the intact animal.