Human myometrium: A new potential source of prolactin

Walters, Clifford A.; Daly, Douglas C.; Chapitis, Jane; Kuslis, Sally T.; Prior, Jerilynn C.; Kusmik, William F.; Riddick, Daniel H.

doi:10.1016/0002-9378(83)90441-6

Cited by 48 publications

(18 citation statements)

References 11 publications

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“…To our knowledge, the presence of GH or its receptors has never been demonstrated in uterus. However, it is known that human myometrium synthesizes decidual-type prolactin [33,34]; prolactin can regulate a number of uterine functions including endometrial proliferation in animals [35,36], and prolactin receptors that can also bind human GH are present in animal uteri [36][37][38][39]. Therefore, the present findings are suggestive of a possible autocrine role for prolactin in human myometrial growth.…”

Section: Discussionmentioning

confidence: 52%

“…Highly purified hCG (1M22 [33], 12 000 IU/mg) with a very low degree of peptide bond nicking (< 3%) was a gift from Professor Wolfgang Merz, University of Heidelberg (Heidelberg, Germany); the polyclonal hCG/LH receptor antibodies raised against synthetic N-terminal rat receptor sequences of 1-11 and 15-38 was from Dr. Patrick Roche of the Mayo Clinic (Rochester, MN); full-length porcine hCG/LH receptor cDNA in pBluescript (SK+) was from Dr. Hugues Loosfelt from Hormones and Reproduction, Hopital de Bicetre (Bicetre, France); and recombinant human epidermal growth factor (EGF) was from Dr. Pablo Valenzuela of Chiron Corp. (Emeryville, CA).…”

Section: Methodsmentioning

confidence: 99%

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Human Myometrial Smooth Muscle Cells are Novel Targets of Direct Regulation by Human Chorionic Gonadotropin1

Környei

Lei

Rao

1993

Biology of Reproduction

102

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Human myometrium contains receptors for hCG/human LH (hLH). This suggested the possibility that hCG and hLH might regulate human myometrium, which has not previously been considered a direct target of gonadotropin regulation. To investigate such a possibility, highly pure and viable smooth muscle cells were isolated from nonpregnant human myometrium and cultured as monolayers. The cells contained hCG/LH receptor mRNA transcripts and a 50-kDa immunoreactive protein that can bind 125I-hCG in a ligand-specific manner. The presence of hCG during culture resulted in a significant increase of myometrial smooth muscle cell density. The hCG effect was time- and concentration-dependent and was mimicked by hLH but not by human FSH or human FSH or human thyroid-stimulating hormone. Human CG also greatly increased the size of a subpopulation of myometrial smooth muscle cells without affecting their chromosomal ploidy. Antibodies to hCG/LH receptors and hCG blocked hCG effects. Human prolactin and growth hormone, which do not bind to hCG/LH receptors, also increased the myometrial smooth muscle cell density. A protein kinase A inhibitor (H-89) blocked hCG response whereas calphostin (a protein kinase C inhibitor) and lavendustin A (a tyrosine kinase inhibitor) had no effect on hCG response, suggesting that a cAMP/protein kinase A signaling mechanism is involved in hCG action. Eicosanoids from cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism are probably not involved, because the inhibitors of these enzymes had no effect on hCG response. While progesterone and estradiol could not mimic or modify hCG action, epidermal growth factor did mimic hCG in increasing myometrial smooth muscle cell density.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 52%

Section: Methodsmentioning

confidence: 99%

Human Myometrial Smooth Muscle Cells are Novel Targets of Direct Regulation by Human Chorionic Gonadotropin1

Környei

Lei

Rao

1993

Biology of Reproduction

102

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“…Taken together, these data provide additional support for the proposed autocrine/paracrine nature of the peptide, and they further indicate that PTHRP gene expression is locally regulated in the uterus. Although myometrial cells are not regarded as classical secretory cells, the myometrium has been previously shown to produce other peptides such as prolactin (37).…”

Section: Discussionmentioning

confidence: 99%

Intrauterine occupancy controls expression of the parathyroid hormone-related peptide gene in preterm rat myometrium.

Thiede

Daifotis

Weir

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

156

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The parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHRP) genes are members of a gene family. Whereas PTH is a classical peptide hormone, mounting evidence suggests that the PTHRP may have predominately local actions. We report here that the PTHRP gene is expressed in rat myometrium, with a major peak in PTHRP mRNA expression occurring in the 48 hr immediately preceding parturition. A similar peak in peptide content was found in tissue extracts by biological and immunological assays, but the PTHRP could not be detected in the peripheral circulation or in uterine vein plasma during late gestation. By in situ hybridization histochemistry, PTHRP mRNA was demonstrated in both the longitudinal and circular layers of smooth muscle but was absent in the endometrium. The rise in myometrial PTHRP mRNA in late gestation was dependent upon intrauterine occupancy; it was greatly reduced or absent in nongravid uterine horns. These findings indicate that the expression of the PTHRP gene in preterm myometrium is under the control of a local stimulus and suggest that the PTIHRP may play a paracrine or autocrine role in the uterus during the antepartum period, possibly involving myometrial contractility.The parathyroid hormone-related peptide (PTHRP) was initially isolated (1-4) and its cDNA cloned (5-8) from human and animal tumors associated with the syndrome of humoral hypercalcemia of malignancy. The PTHRP has sequence similarity to parathyroid hormone (PTH) at its N terminus, which appears to account for its PTH-like actions when it is secreted into the systemic circulation by malignant tumors (9). However, the deduced PTHRP product is larger than PTH and has a more complex structure, suggesting that it may be subject to one or several posttranslational processing steps (5-8). The precise secretory form of the PTHRP has not been established for any cell type.Chromosomal localization studies and the structures of the PTH and PTHRP genes indicate that they arose by duplication from a common ancestral chromosome (10-12). Following this duplication event, the two genes have clearly evolved separately. The human PTHRP gene has been found to have an organization that is considerably more complex than that of the PTH gene (10)(11)(12)(13)(14). In addition, whereas the PTH gene is expressed predominately if not exclusively in parathyroid cells (15), the PTHRP gene is widely expressed in both endocrine and nonendocrine tissues. These sites of expression include tissues as diverse as skin (6,16,17), lactating mammary tissue (8), the chicken oviduct shell gland (18), the endocrine pancreas (19), and regions of the central nervous system (20). The role(s) of the PTHRP in these various sites is unknown, but the available evidence suggests that the peptide may be acting locally. Unique PTHRP receptors have not yet been identified.We report here that the PTHRP gene is expressed in rat myometrium and that this expression peaks in the antepartum period. This peak in PTHRP gene expression is confined to gravid ute...

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“…Although initially identified as a pituitary gland hormone, several studies have demonstrated that prolactin is also produced by uterine tissues, including the endometrium, myometrium, and uterine leiomyomas (Daly et al 1984;Maslar and Riddick 1979;Walters et al 1983). The significance of prolactin production in leiomyomas is not yet well defined; however, interest in this hormone has been stimulated by the finding that prolactin acts as a mitogen for vascular smooth muscle (Sauro and Zorn 1991).…”

Section: Growth Factors Identified In Fibroidsmentioning

confidence: 99%

Etiology and pathogenesis of uterine leiomyomas: a review.

Flake

Andersen

Dixon

2003

Environ Health Perspect

496

392

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Uterine leiomyomas, or fibroids, represent a major public health problem. It is believed that these tumors develop in the majority of American women and become symptomatic in one-third of these women. They are the most frequent indication for hysterectomy in the United States. Although the initiator or initiators of fibroids are unknown, several predisposing factors have been identified, including age (late reproductive years), African-American ethnicity, nulliparity, and obesity. Nonrandom cytogenetic abnormalities have been found in about 40% of tumors examined. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has only recently been explored. Growth factors with mitogenic activity, such as transforming growth factor-β 3, basic fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I, are elevated in fibroids and may be the effectors of estrogen and progesterone promotion. These data offer clues to the etiology and pathogenesis of this common condition, which we have analyzed and summarized in this review.

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Human myometrium: A new potential source of prolactin

Cited by 48 publications

References 11 publications

Human Myometrial Smooth Muscle Cells are Novel Targets of Direct Regulation by Human Chorionic Gonadotropin1

Human Myometrial Smooth Muscle Cells are Novel Targets of Direct Regulation by Human Chorionic Gonadotropin1

Intrauterine occupancy controls expression of the parathyroid hormone-related peptide gene in preterm rat myometrium.

Etiology and pathogenesis of uterine leiomyomas: a review.

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