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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary and plasma pools from postmenopausal women and plasma pools from women at midcycle were fractionated by electrofocusing in sucrose density gradients. The biological LH activity was determined in each of the electrofocusing fractions by the use of an in vitro bioassay method. A heterogeneous profile of LH activity was found in both pituitary and plasma samples with a large proportion present within the pH range 6.5-10. In a total of 11 electrofocusing runs 7 main regions of high LH activity were found within this range with mean pI values (+/- SD) of 6.75 +/- 0.08 (n = 6), 7.33 +/- 0.08 (11), 7.80 +/- 0.09 (11), 8.23 +/- 0.10 (11), 8.81 +/- 0.04 (7), 9.17 +/- 0.05 (6) and 9.55 (2). A significantly higher proportion of LH activity was found in the midcycle plasma samples (36%) in the pH regions with mean pI values of 8.81, 9.17 and 9.55 than in postmenopausal plasma (7%) and pituitary extracts (5%). This indicates that the profile of biologically active LH in women in the fertile age is different from that present in postmenopausal women. By detailed fractionation based on narrow pH range studies and the refocusing of specific peak fractions it was shown that each of the regions studied consisted of several peaks of LH activity indicating the presence of a large number of molecular species exhibiting varying degrees of LH activity. The relative proportions of these species showed considerable differences between sources but also between samples from the same source.
Mol Cell Endocrinol 1977 Nov
PMID:Biological and immunological characterization of human luteinizing hormone: I. Biological profile in pituitary and plasma samples after electrofocusing. 2 70

The incorporation of labeled amino acids and glucosamine into LH and FSH by cultured rat anterior pituitary cells and anterior pituitary homogenates is reported. There was a significant augmentation in this incorporation by cells after 6 days of culture in the presence of GnRH. Tritiated LH and FSH were found in the cell extracts as well as in the media by the method of immunoprecipitation. An increase of approximately 7--13-fold in the release of LH and FSH into the cell incubation medium was observed in the presence of GnRH (3 ng/ml). The rate of incorporation of [3H]proline was higher than that of [3H]glucosamine into LH and FSH. At the same time a higher incorporation of labeled amino acids was observed in the case of FSH than with LH. Cycloheximide inhibited completely the incorporation of labeled proline but the inhibition was partial for the incorporation of labeled glucosamine. Freshly dispersed cells, short-time cultures maintained for 20 h and pituitary homogenates also incorporated labeled amino acids into LH and FSH, but GnRH had no effect on this incorporation. Pituitary homogenates also incorporated [3H]glucosamine into LH and FSH with an optimal incorporation after 30 min of incubation. Three different concentrations of GnRH had no effect on the incorporation of [3H]proline by homogenates. Cycloheximide and puromycin inhibited this incorporation completely.
Mol Cell Endocrinol 1978 Oct
PMID:Biosynthesis of gonadotropins by rat pituitary cells in culture and in pituitary homogenates: effect of gonadotropin-releasing hormone. 36 88

The first IRP of Human Pituitary Gonadotrophins (FSH/LH) for bioassay (69/104) and the 1st IRP of Human Pituitary Luteinizing Hormone (LH) for immunoassay (68/40) were fractionated by an electrofocusing technique in a sucrose density gradient and the profile of biological and immunological activities was determined. The partially purified LH preparation (69/104) gave a broad pattern of biolgical and immunological activities which extended from pH 4 to 10. The biological : immunological (B/I) ratio of the various fractions (using the 68/40 preparation as standard) ranged from 0.04 to 1.05. The low B/I ratios indicate the presence of high levels of immunologically active, biologically inactive material in this preparation. In contrast to the behaviour of the 69/104 preparation, the major proportion (88%) of the biological activity recovered after electrofocusing of the highly purified LH preparation (68/40) was found within the pH range 7--9, with B/I ratios (again using as standard the 68/40 preparation) ranging from 0.4 to 1.5. Multiple dose parallel line design radioimmunoassays revealed a lack of parallelism between the 69/104 and 68/40 International Reference Preparations. This was attributed to the presence of acidic material in the former preparation, which is practically absent from the latter. The biological LH profiles of both the 69/104 and 68/40 preparations differed from those previously reported for aqueous extracts of pituitaries. It is concluded that the dissimilarity in the electrofocusing profiles of the biological and immunological activities of the 69/104 preparation renders this preparation unsuitable as a reference preparation for the quantitation of biologically active LH by radioimmunoassay methods. Using the same criteria, the 68/40 preparation would appear to be a more suitable standard.
Mol Cell Endocrinol 1978 Jun
PMID:Biological and immunological characterization of human luteinizing hormone: IV. Biological and immunological profile of two international reference preparations after electrofocusing. 68 Mar 37

Pituitary glands of ovariectomized rats were incubated for four hours and the LH released into the medium was measured by radioimmunoassay at one-hour intervals. The effect of a maximally active dose of LH-RH (1000 mg/ml) on pituitary LH release was inhibited by oestradiol (15 ng/ml) added to the media. Although cycloheximide (25 mug/ml) and puromycin (54 mug/ml) in the medium did not affect LH-RH-induced LH release consistently, the inhibitory effect of oestradiol was prevented. It is concluded that this effect of oestradiol is dependent on de novo synthesis of protein.
Mol Cell Endocrinol 1976 May
PMID:Absence of an inhibitory effect of oestradiol on LH-RH induced release of LH in vitro caused by inhibition of protein synthesis. 78 Jan 72

Pituitary lactotroph cell function and PRL gene expression are highly regulated by the cAMP-protein kinase-A (PKA) pathway. To further our understanding of the molecular mechanisms by which cAMP/PKA regulates rat (r) PRL promoter activity and to determine whether cAMP regulation is cell type specific, we 1) transected intact (-425), internal and 5'-deletion, and site-specific mutants of the rPRL promoter ligated to the firefly luciferase reporter gene into both pituitary and nonpituitary cell lines; and 2) assessed the role of the cAMP-cAMP response element-binding protein (CREB) pathway in GH4 rat pituitary cells. The data show that deleting the rPRL promoter from -425 to -116 did not abolish cAMP regulation, implying that proximal elements, such as the basal transcription element (-112/-80) or the pituitary-specific footprint (FP) I (-67/-45), mediate the cAMP response. However, nucleotide changes within FP I or FP II (-130/-120) did not alter the rPRL promoter response to 1 microM forskolin (FSK), despite the 77% and 26% reductions in basal rPRL promoter activity caused by these mutations, respectively. Furthermore, internal deletion of either the basal transcription element of FP I element also failed to affect cAMP regulation of the rPRL promoter, again despite the 90% and 93% reductions in basal promoter activity by these deletions, respectively. Since these internal deletion constructs otherwise contain rPRL promoter sequences from -425 to +73, including the up-stream pituitary-specific FPs III and IV, the data suggest that any one of these cell-specific elements is capable of imparting cAMP regulation to the proximal rPRL promoter. To directly test the implication that the cAMP response of the rPRL promoter is restricted to the pituitary-specific cell type, we took advantage of a 5'-deletion mutant truncated at position -116 and a FP II site-specific mutant, since constructs containing these rPRL promoters are active in nonpituitary cells. Despite the 6.6- and 18.5-fold stimulations over wild-type rPRL promoter activity in nonpituitary cells, respectively, these mutations remained completely unresponsive to FSK treatment. To document that the cAMP-CREB pathway was functional in GC/GH4 rat pituitary cells, CREB was affinity purified from GC rat pituitary cells, and DNase-I protection studies showed that it does not bind to the proximal rPRL promoter. Also, the human glycoprotein alpha-subunit promoter was induced 10-fold by FSK in GH4 rat pituitary cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Endocrinol 1992 Dec
PMID:Cyclic adenosine 3',5'-monophosphate activation of the rat prolactin promoter is restricted to the pituitary-specific cell type. 133 42

The modulation of FSH secretion at the beginning and middle of the follicular phase of the cycle represents the key event in the growth and selection of the preovulatory follicle. However, the mechanisms that operate within the pituitary gland to control the increased release of FSH and its subsequent inhibition in vivo remain unclear. Treatment of ewes with bovine follicular fluid (bFF) during the luteal phase has been previously shown to suppress the plasma concentrations of FSH and, following cessation of treatment on day 11, a rebound release of FSH occurs on days 12 and 13. When luteal regression is induced on day 12, this hypersecretion of FSH results in an increase in follicle growth and ovulation rate. To investigate the mechanisms involved in the control of FSH secretion, ewes were treated with twice daily s.c. injections of 5 ml bFF on days 3-11 of the oestrous cycle and luteal regression was induced on day 12 with prostaglandin (PG). The treated ewes and their controls were then killed on day 11 (luteal), or 16 or 32 h after PG and their pituitaries removed and halved. One half was analysed for gonadotrophin and gonadotrophin-releasing hormone (GnRH) receptor content. Total pituitary RNA was extracted from the other half and subjected to Northern analysis using probes for FSH-beta, LH-beta and common alpha subunit. Frequent blood samples were taken and assayed for gonadotrophins. FSH secretion was significantly (P less than 0.01) reduced during bFF treatment throughout the luteal phase and then significantly (P less than 0.01) increased after cessation of treatment, with maximum secretion being reached 18-22h after PG, and then declining towards control values by 32h after PG. A similar pattern of LH secretion was seen after bFF treatment. Pituitary FSH content was significantly (P less than 0.05) reduced by bFF treatment at all stages of the cycle. No difference in the pituitary LH content was seen. The increase in GnRH receptor content after PG in the controls was delayed in the treated animals. Analysis of pituitary mRNA levels revealed that bFF treatment significantly (P less than 0.01) reduced FSH-beta mRNA levels in the luteal phase. Increased levels of FSH-beta, LH-beta and alpha subunit mRNA were seen 16h after PG in the bFF-treated animals, at the time when FSH and LH secretion from the pituitary was near maximum.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Endocrinol 1992 Apr
PMID:Relationship between gonadotrophin subunit gene expression, gonadotrophin-releasing hormone receptor content and pituitary and plasma gonadotrophin concentrations during the rebound release of FSH after treatment of ewes with bovine follicular fluid during the luteal phase of the cycle. 138 Nov 79

Hypogonadal (hpg) mutant mice, with a congenital deficiency of hypothalamic gonadotrophin-releasing hormone (GnRH), and testicular feminized (tfm) mice, which lack a functional androgen receptor, were used to study the effects of the potent GnRH agonist 'Zoladex' (ICI 118630; D-Ser (Bu(t))6, Azgly10-GnRH) on pituitary and gonadal function. Zoladex (0.5 mg) in a sustained-release lactide-glycolide copolymer depot was administered subcutaneously under anaesthesia and was left in place for 7 days, after which time the effects of the drug upon pituitary and serum gonadotrophin concentrations, glycoprotein hormone subunit mRNAs and testicular morphology were investigated. At the pituitary level, Zoladex treatment resulted in a substantial reduction in LH content in normal males, and LH content was depressed in hpg mice even below the basal levels normally found in these mutants. Pituitary LH content in the Zoladex-treated animals was depressed in the tfm groups, but not to the same levels as those found in the normal and castrated normal mice. Zoladex treatment at the time of castration prevented the post-operative elevation in serum LH associated with castration alone. In the androgen-deficient tfm mouse, Zoladex did not depress the normally elevated serum LH levels. Serum LH in the hpg animals was, in all cases, below the limit of detection of the assay. Pituitary FSH content was depressed into the hpg range in both the normal and castrated animals, but there was no further depression in the hpg mice. The pituitary content was reduced in the tfm mice, again the effects not being as dramatic as in the normal and castrated animals. Serum FSH content, as measured by radioimmunoassay, was depressed by 50% in normal mice; there was no reduction in the hpg mice, however. With regard to pituitary gonadotrophic hormone gene expression, Zoladex administration to normal mice caused a dramatic reduction in LH beta mRNA content, to a level approximating that found in untreated hpg mice. The drug also depressed LH beta mRNA in the castrated group to the hpg range when given at the time of castration, whereas in untreated castrated mice there was a significant increase in LH beta mRNA. In the tfm mouse, which can be considered as a model for long-term failure of androgen feedback, Zoladex again induced a fall in LH beta mRNA, but not to the same extent as in the normal and normal castrated group. Zoladex had no effect on the already low levels of LH beta mRNA found in hpg mice.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Endocrinol 1992 Jun
PMID:Effects of the gonadotrophin-releasing hormone agonist 'Zoladex' upon pituitary and gonadal function in hypogonadal (hpg) male mice: a comparison with normal male and testicular feminized (tfm) mice. 138 60

In ovariectomized estrogen-primed rats, progesterone as well as 5 alpha-dihydroprogesterone (5 alpha-DHP) are capable of inducing the release of gonadotropins. This study examined the need of 5 alpha-reduction as a prerequisite for the action of progesterone. The 5 alpha-reductase inhibitor, N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide was injected at a 1 or 2 mg dose/rat 2 h prior to an injection of 0.4 or 0.8 mg progesterone/kg body weight at 0900 h to immature ovariectomized, estrogen-primed rats and serum was analyzed for LH and FSH at 1500 h. Pituitary and hypothalamic 5 alpha-reductase activity was measured at the time of progesterone administration and at the time of the surge by incubating tissue homogenates with [3H]progesterone. Substrate, ([3H]progesterone) and product ([3H]5 alpha-DHP), were separated by reverse phase HPLC. The pituitary 5 alpha-reductase activity was not blocked at 1500 h. However, both pituitary and hypothalamic 5 alpha-reductase was blocked at the time of progesterone administration. No effect was seen by acute administration of the 5 alpha-reductase inhibitor upon either the 0.4 or 0.8 mg progesterone/kg-induced release of LH and FSH. There was, however, a specific, significant inhibition of progesterone-induced FSH but not LH release when the 5 alpha-reductase inhibition was sustained throughout the afternoon of the gonadotropin surge. These results indicate a biologically significant role for the irreversible 5 alpha-reduction of progesterone in the modulation of the release of FSH.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Role of 5 alpha-reduction in progesterone's ability to release FSH in estrogen-primed ovariectomized rats. 138 45

Prodynorphin is expressed by neurons of the hypothalamus and gonadotrophs of the anterior pituitary gland (AP) and plays a role in the negative feedback regulation of the reproductive neuroendocrine axis. The present study examined whether gonadal steroid hormones are capable of modulating pituitary prodynorphin expression in immature, female rats. Steroids were administered via subcutaneous Silastic implants and rats were killed at 29 days of age. Northern blot analysis was used to measure AP prodynorphin, luteinizing hormone-beta (LH beta), follicle-stimulating hormone-beta (FSH beta), and common alpha-subunit mRNA levels (normalized to 18S ribosomal RNA). Treatment groups (n = 5-6) consisted of control (CNT; empty implants), estradiol (E2; 4 days), E2 + progesterone (E2 + P4; 8 days and 4 days, respectively), and dihydrotestosterone (DHT; 4 days). Pituitary prodynorphin mRNA was significantly suppressed in only the DHT-treated animals (26 +/- 10% of CNT, p < 0.01). LH beta mRNA was suppressed by all steroid treatments (p < 0.01), FSH beta was lower in only the E2 group, and alpha-subunit was reduced in both the E2 + P4 and DHT groups (p < 0.01). Serum LH was suppressed by all steroid treatments but FSH was reduced in only the E2 and E2 + P4 groups (p < 0.01). Treatment of prepubescent rats with continuous high levels of gonadal steroids is known to severely reduce endogenous hypothalamic gonadotropin releasing hormone (GnRH) release and this is supported by our observation of reduced gonadotropin-subunit gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Oct
PMID:Differential regulation of anterior pituitary prodynorphin and gonadotropin-subunit gene expression by steroid hormones. 145 42

LH, FSH, and TSH are heterodimeric glycoprotein hormones composed of a common alpha-subunit and unique beta-subunits. The alpha-subunit is produced in two distinct specialized cell types of the pituitary gland: gonadotropes, which synthesize LH and FSH, and thyrotropes, which synthesize TSH. We have demonstrated that 313 base pairs of the bovine-alpha subunit promoter direct expression of diphtheria toxin A chain specifically to the gonadotropes in transgenic mice. Animals carrying this transgene generally exhibit reproductive failure and lack of gonadal differentiation, consistent with gonadotrope ablation. Lack of gonadotrope activity was verified by RIA and immunohistochemical staining for LH. The phenotype of these transgenic mice is nearly identical to mice homozygous for the spontaneous mutation, hpg, which is due to a deletion in the gene encoding GnRH. Thyrotrope function was judged normal based on overall growth of the animals, appearance of their thyroids, T4 levels measured by RIA, and immunohistochemical staining for TSH. The ablation of gonadotropes but not thyrotropes suggests that separate cis-acting elements are necessary for expression of the alpha-subunit gene in these two cell types. Pituitary content of ACTH and GH was apparently normal, while PRL synthesis and storage were reduced. Thus, in a pituitary almost completely devoid of gonadotropes, most other pituitary functions were normal. This suggests that most pituitary cells are able to differentiate independently of terminal gonadotrope differentiation and can function in the absence of paracrine signaling provided by gonadotropes.
Mol Endocrinol 1991 Dec
PMID:Targeted ablation of pituitary gonadotropes in transgenic mice. 166 5


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