CHANGES IN RESPONSIVENESS OF DISPERSED PITUITARY CELLS TO LUTEINIZING HORMONE RELEASING HORMONE AT DIFFERENT TIMES OF THE OESTROUS CYCLE OF THE RAT

1981 ◽  
Vol 89 (1) ◽  
pp. 129-134 ◽  
Author(s):  
ALISON SPEIGHT ◽  
G. FINK
Keyword(s):  
Luteinizing Hormone ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Pituitary Cells ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Close Relationship ◽  
Specific Receptors ◽  
Lh Rh

Dispersed pituitary cells obtained from female rats with regular oestrous cycles were suspended in Bio-Gel columns and perfused with pulses of luteinizing hormone releasing hormone (LH-RH). There was a close relationship between the amount of LH released and the concentration of LH-RH in the perfusate. It was not possible to elicit the priming effect of LH-RH, but the LH-response changed markedly during the oestrous cycle in a manner similar to that seen in vivo; i.e. the responses of cells prepared from rats killed at pro-oestrus were much greater than the responses of cells prepared from rats killed on other days of the cycle. A similar change in responsiveness was obtained when the columns were perfused with 60 mmol K+/1, suggesting that at least part of the increase in pituitary responsiveness that occurs at pro-oestrus is not dependent upon changes in specific receptors for LH-RH.

EFFECT OF SYNTHETIC LUTEINIZING HORMONE RELEASING HORMONE ON OVULATION DURING THE OESTROUS CYCLE IN THE RAT

1974 ◽  
Vol 76 (3) ◽  
pp. 431-437 ◽  
Author(s):  
H. Morishita ◽  
H. Mitani ◽  
Y. Masuda ◽  
K. Higuchi ◽  
M. Tomioka ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Pituitary Gland ◽  
Critical Period ◽  
Early Period ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Average Volume ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lh Rh

ABSTRACT The effect of synthetic luteinizing hormone releasing hormone (LH-RH) on ovulation has been studied during the oestrous cycle in adult female rats. Ovulation could be induced by the administration of 1 μg synthetic LH-RH at 1:00 a. m. on the day of dioestrus II (lights on from 10:00 p.m. to 10:00 a.m.). At 1:00 a.m. on the day of dioestrus II, the average volume of the largest follicles reached a volume of 83 × 106 μm3 and was three fifth of the volume of that at 6:00 a. m. on the day of pro-oestrus (critical period). These findings suggest that the luteinizing hormone (LH) content in the pituitary gland during the early period of dioestrus II is sufficient to induce ovulation and that the follicles that reach to three fifth of the volume at the critical period are capable of ovulating providing endogenous ovulatory LH released.

Evolution of Design and Achievement of Inhibitors of the Luteinizing Hormone-Releasing Hormone as Inhibitors of Ovulation

1982 ◽  
Vol 37 (2) ◽  
pp. 246-259 ◽  
Author(s):  
Karl Folkers ◽  
John Humphries ◽  
Cyril Y. Bowers
Keyword(s):  
Luteinizing Hormone ◽  
Adult Male ◽  
Subcutaneous Tissue ◽  
Female Rats ◽  
Male Rats ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lh Rh

Abstract Detailed structure-activity studies on inhibitors of the luteinizing hormone releasing hormone (LH-RH) have been described. The most potent ovulation inhibitors have substitutions in positions 1, 2, 3, and 6. Currently four basic structural requirements for potent antiovulatory activity are: a D-aromatic amino acid, such as D-Trp or D-Phe, in position 6; a D-Phe residue in position 2; substitutions in positions 1 and 3. For inhibitors based on substitutions in positions 2, 3, and 6, the substitution of a Pro, N-Me-Leu or D-Trp residue in position 3 is equally acceptable, and gives analogues which inhibit ovulation at 750 ^g/rat. For inhibitors based on substitutions in positions 1, 2, 3, and 6, D-Trp appears necessary in position 3 in order for ovulation to be inhibited at 200 μ/rat. Many analogues based on the [residue1, D-Phe2, D-Trp3, D-Trp6]-LH-RH sequence are known which inhibit ovulation at 200 μ/rat. These include those analogues having D- <Glu, Ac-Pro, N-Ac-Hyp and N-Ac-Thr in position 1. The choice between L- or Dresidues in this position is structure dependent (Ac-L-Pro > Ac-D-Pro, D- <Glu >L- <Glu, etc.). In addition, a "protected" N-terminal residue having some polar character appears to be important. Substitution of the dipeptide residue, <Glu-Pro-, into position 1 has produced a new category of potent ovulation inhibitors based on linear peptides longer than decapeptides. Continued studies on other analogues in this later class could provide more potent inhibitors by (1) utilizing new binding sites on or in the vicinity of the LH-RH receptor(s); (2) altering transportation properties; (3) producing "pro-drugs". The substitution of N-Me-Leu into position 7 was not advantageous, presumably because of the presence of bulky D-aromatic amino acids in position 6. Nonapeptide ethylamide analogues also had very low antiovulatory potencies. The analogue [chlorambucil1, Leu2, Leu3, D-Ala6]-LH-RH acted as an agonist, but also inhibited in a modified assay in vitro. Comparative assays measuring the inhibition of LH-RH, and inhibition of ovulation have emphasized other factors of importance to inhibitor design. Although all ovulation inhibitors active at 750 or 200 /μg/rat strongly inhibited in vivo, at a ratio of analogue to LH-RH of 166:1, other analogues of comparable in vitro potency have displayed a range of antiovulatory activities. Similar discrepancies have been observed in the results of in vivo LH-RH inhibition assays. The most potent ovulation inhibitors always inhibited LH-RH at 333:1 in adult male chimpanzees, and at 100:1 in adult male rats. The dissociation of the results of the LH-RH and antiovulatory assays have been rationalized in two cases. The Cpc-analogues were active in inhibiting LH-RH in rats and in chimpanzees when given i.V., but were inactive in rats when given s.c. which is the mode of administration in the antiovulatory assay. The results for inhibition of LH-RH in vivo paralleled the results for inhibition of ovulation, and raised a question as to differences in absorption of peptides though the lipid layers of subcutaneous tissue. The reduced in vivo activities of the L-Trp3 analogues in both the LH-RH and antiovulatory assays suggest an increase in enzymatic inactivation for these compounds. [D-Phe2, Pro3, D-Phe6]-LH-RH can inhibit endogenous LH-RH in the Rhesus monkey and inhibit ovulation. Infusion of [D-Phe2, Pro3, D-Trp6]-LH-RH at 375 ^ug/day for 4 days from a s.c. implanted minipump completely inhibited ovulation in cycling female rats and decreased serum LH levels in castrated rats. In contrast with LH-RH or des-Gly10- [D-Ala6]-LH-RH ethylamide the Pro3 analogue did not block uterine implantation sites of mated rats, indicating a difference in the mechanism of contraception for LH-RH agonists and inhibitors

PROLONGED RELEASE BY DIOESTROUS RATS OF FOLLICLE-STIMULATING HORMONE DURING THE PERIOD OF OVULATION INDUCED BY LUTEINIZING HORMONE RELEASING HORMONE

1979 ◽  
Vol 81 (1) ◽  
pp. 109-118 ◽  
Author(s):  
SHUJI SASAMOTO ◽  
SHIGEO HARADA ◽  
KAZUYOSHI TAYA
Keyword(s):  
Luteinizing Hormone ◽  
Plasma Concentrations ◽  
High Plasma ◽  
Oestrous Cycle ◽  
Prolonged Release ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Follicular Maturation ◽  
Lh Rh ◽  
Premature Ovulation

When 1·0 μg luteinizing hormone releasing hormone (LH-RH) was given i.v. three times at 1 h intervals from 17.00 to 19.00 h on the day of dioestrus (day 0) to regular 4 day cyclic rats, premature ovulation was induced the next morning (day 1) with the number of ova present comparable to normal spontaneous ovulation. The next spontaneous ovulation occurred on the morning of day 5, 4 days after premature ovulation induced by LH-RH. Plasma concentrations of FSH and LH showed transient rises and falls within 1 h of administration of LH-RH; concentrations of FSH in the plasma decreased from 20.00 h on day 0 but markedly increased again from 23.00 h on day 0 to 02.00 h on day 1 and these high levels persisted until 14.00 h on day 1, with only a small increase of plasma LH during this period. The duration of increased FSH release during premature ovulation induced by LH-RH treatment was 6 h longer than the FSH surge occurring after administration of HCG on day 0. Surges of gonadotrophin were absent on the afternoon of day 1 (the expected day of pro-oestrus) and the surges characteristic of pro-oestrus occurred on the afternoon of day 4 and ovulation followed the next morning. The pituitary content of FSH did not decrease despite persisting high plasma levels of FSH during premature ovulation induced by either LH-RH or HCG on day 0. The changes in uterine weight indicated that the pattern of oestrogen secretion from the day of premature ovulation induced by LH-RH to the day of the next spontaneous ovulation was similar to that of the normal 4 day oestrous cycle. When 10 i.u. HCG were given on day 0, an increase in oestrogen secretion occurred on day 2, 1 day earlier than in the group given LH-RH on day 0. This advancement of oestrogen secretion was assumed to be responsible for the gonadotrophin surges on day 3. Similar numbers of fully developed follicles were found by 17.00 h on day 2 after premature ovulation induced by either LH-RH or HCG, suggesting that the shorter surge of FSH during premature ovulation induced by HCG had no serious consequences on the initiation of follicular maturation for the succeeding oestrous cycle in these rats. Administration of LH-RH on day 0 had no direct effect on the FSH surge during premature ovulation. Secretory changes in the ovary during ovulation may be responsible for this prolonged selective release of FSH.

INHIBITION BY MELATONIN OF THE PITUITARY RESPONSE TO LUTEINIZING HORMONE RELEASING HORMONE IN VIVO

1978 ◽  
Vol 76 (3) ◽  
pp. 487-491 ◽  
Author(s):  
K. YAMASHITA ◽  
M. MIENO ◽  
T. SHIMIZU ◽  
ER. YAMASHITA
Keyword(s):  
Luteinizing Hormone ◽  
Carotid Artery ◽  
Anterior Pituitary ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lh Rh ◽  
Lh Secretion

The rate of secretion of 17-oxosteroids by the testes of anaesthetized dogs in vivo was used as an index of LH secretion. Intracarotid injection of luteinizing hormone releasing hormone (LH-RH, 1, 5 or 10 μg/kg body wt) resulted in an increase in the testicular 17-oxosteroid secretion which was roughly proportional to the dose administered and which reached a maximum 60 min after the injection. Testicular output of 17-oxosteroids was unaffected by administration of melatonin (10 or 100 μg/kg body wt) into the carotid artery. When LH-RH (5 μg/kg) was injected into the carotid artery 3 h after intracarotid injection of melatonin (10 or 100 μg/kg), the testicular response to LH-RH was considerably diminished. Pretreatment with melatonin (100 μg/kg) did not alter the testicular response to human chorionic gonadotrophin (20 i.u./kg body wt) given i.v. It is concluded that melatonin may act directly on the anterior pituitary gland in dogs to inhibit the LH-RH-induced release of LH.

SERUM LUTEINIZING HORMONE AND FOLLICLE-STIMULATING HORMONE CONCENTRATIONS IN IMMATURE FEMALE RATS TREATED WITH MULTIPLE INJECTIONS AND VARIOUS AMOUNTS OF LUTEINIZING HORMONE RELEASING HORMONE

1975 ◽  
Vol 66 (1) ◽  
pp. 13-20 ◽  
Author(s):  
D. C. JOHNSON ◽  
R. S. MALLAMPATI
Keyword(s):  
Luteinizing Hormone ◽  
Constant Stimulus ◽  
Female Rats ◽  
Intact Female ◽  
Immature Female ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Serum Luteinizing Hormone ◽  
Serum Lh ◽  
Lh Rh

SUMMARY Release of immunoreactive LH and FSH was induced in immature intact female rats by repeated injections of synthetic luteinizing hormone releasing hormone (LH-RH). Altering the dose of LH-RH (5, 10, 20, 50 ng) and the frequency of administration (every 10, 20, 30 or 60 min) over a period of 2 h produced a variety of serum LH and FSH concentrations and ratios. When the dose was a constant 20 ng but the frequency of injections was either 20 or 30 min, a steady state in serum gonadotrophin concentrations was reached within 1 h and the level remained the same during the second hour. When given every 10 min, 20 ng LH-RH produced a much higher concentration of both LH and FSH during the second hour of stimulation. Examination of the gonadotrophin levels after each injection of LH-RH showed that the pituitary response was variable in spite of a constant stimulus.

Stimulatory effect of thyrotrophin-releasing hormone (TRH) on the release of luteinizing hormone (LH) from rat anterior pituitary cells in vitro

1983 ◽  
Vol 61 (2) ◽  
pp. 186-189 ◽  
Author(s):  
Noboru Fujihara ◽  
Masataka Shiino
Keyword(s):  
Luteinizing Hormone ◽  
Anterior Pituitary ◽  
Pituitary Cells ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Anterior Pituitary Cells ◽  
Lh Release ◽  
Lh Rh

The effect of thyrotrophin-releasing hormone (TRH, 10−7 M) on luteinizing hormone (LH) release from rat anterior pituitary cells was examined using organ and primary cell culture. The addition of TRH to the culture medium resulted in a slightly enhanced release of LH from the cultured pituitary tissues. However, the amount of LH release stimulated by TRH was not greater than that produced by luteinizing hormone – releasing hormone (LH–RH, 10−7 M). Actinomycin D (2 × 10−5 M) and cycloheximide (10−4 M) had an inhibitory effect on the action of TRH on LH release. The inability of TRH to elicit gonadotrophin release from the anterior pituitary glands in vivo may partly be due to physiological inhibition of its action by other hypothalamic factor(s).

STIMULATION OF RELEASE OF LUTEINIZING HORMONE FROM CULTURED PITUITARY CELLS BY 2- AND 4-HYDROXYLATED OESTROGENS

1981 ◽  
Vol 90 (3) ◽  
pp. 433-436 ◽  
Author(s):  
S. FRANKS ◽  
G. R. MERRIAM ◽  
CYNTHIA G. GOODYER ◽  
F. NAFTOLIN
Keyword(s):  
Luteinizing Hormone ◽  
Anterior Pituitary ◽  
Monolayer Culture ◽  
Pituitary Cells ◽  
Releasing Hormone ◽  
Oestradiol Treatment ◽  
Lh Rh ◽  
Lh Releasing Hormone ◽  
Stimulation Of

We have examined the effects of the catechol oestrogens 2-hydroxyoestradiol (2-OHE2), 4-hydroxyoestradiol (4-OHE2) and 2-hydroxyoestrone (2-OHE1) and their corresponding primary oestrogens on secretion of LH and FSH by enzymatically dispersed rat anterior pituitary cells in monolayer culture. Basal LH levels in the medium were significantly higher than in control wells when cells were exposed to 10−8m-oestradiol-17β for 40 h: oestrone and all three catechol oestrogens (in the same doses) also stimulated basal LH concentrations to levels quantitatively similar to those seen after oestradiol treatment. The same effects were observed when steroids were given at 10−9 mol/l. Oestradiol, 2-OHE2, and 4-OHE2 but not 2-OHE1 increased pituitary responsiveness to LH releasing hormone (LH-RH) (given in a range of doses from 10−11 to 10−6 mol/l). The responses of cells treated with 2-OHE2 and 4-OHE2 were similar, though less than the response seen after treatment with oestradiol. This contrasts with the very different oestrogenic effects of 2- and 4-OHE2 previously observed in vivo. Neither oestradiol nor the catechol oestrogens had any effect on basal or LH-RH-stimulated FSH release.

STIMULATION OF PROSTAGLANDIN ACCUMULATION IN THE RAT ANTERIOR PITUITARY GLAND BY LUTEINIZING HORMONE RELEASING HORMONE IN VITRO

1977 ◽  
Vol 75 (2) ◽  
pp. 277-283 ◽  
Author(s):  
N. BARDEN ◽  
A. BETTERIDGE
Keyword(s):  
Luteinizing Hormone ◽  
Cyclic Amp ◽  
Anterior Pituitary ◽  
Pituitary Cells ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lh Release ◽  
Lh Rh ◽  
Stimulation Of

The addition of luteinizing hormone releasing hormone (LH-RH) to cultures of monolayers of rat anterior pituitary cells was shown to increase both the concentrations of prostaglandins E1 and E2 (PGE) in the cells and the release of LH over similar ranges of concentrations of LH-RH (10−6 to 10−10 mol/l). The peak concentration of PGE was observed after 2·5 h. The stimulation of the level of PGE in the cells by LH-RH was completely inhibited by two inhibitors of prostaglandin synthetase, which only partially inhibited the stimulation of LH release. Therefore the increased concentration of PGE was not obligatory for the effect of LH-RH on LH release. It was also shown that monobutyryl cyclic AMP stimulated the intracellular concentration of PGE and it is suggested that the stimulation of PGE levels may be mediated by increased levels of cyclic AMP in the cells after the addition of LH-RH.

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