Follicle-Stimulating Hormone Increases the Expression of Tissue Inhibitors of Metalloproteinases TIMP-1 and TIMP-2 and Induces TIMP-1 AP-1 Site Binding Complex(es) in Prepubertal Rat Sertoli Cells

Salvatore Ulisse, Antonietta R. Farina, Deamaria Piersanti, Antonella Tiberio, Lucia Cappabianca, Gabriella D'Orazi, Emmanuele A. Jannini, Olga Malykh, William G. Stetler-Stevenson, Massimino D'Armiento, Alberto Gulino, Andrew R. Mackay

Research output: Contribution to journalArticle

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Abstract

Primary cultures of prepubertal rat Sertoli cells secrete two major tissue inhibitors of metalloproteinases: TIMP-1 (M, 28 K) and TIMP-2 (Mr 21 K). FSH stimulated Sertoli cell TIMP-1 and TIMP-2 activity in a time- and dose-dependent manner and also stimulated TIMP-1 and TIMP-2 protein and messenger RNA levels. These effects were mimicked by the cAMP analog, 8-bromo-cAMP, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. The protein kinase C activating phorbol ester phorbol myristrate acetate (TPA) stimulated TIMP-1 but not TIMP-2 activity and messenger RNA levels. Cycloheximide and actinomycin-D inhibited basal TIMP-1 and TIMP-2 activity and inhibited the ability of FSH, 8-bromo-cAMP, and TPA to stimulate TIMP activity. The protein kinase A (PKA) inhibitor AMP Rp isomer did not affect basal TIMP-1 and TIMP-2 activity or TPA-stimulated TIMP-1 activity. However, the PKA inhibitor markedly reduced FSH and 3-isobutyl-1-methylxanthine stimulation of TIMP-1 and TIMP-2 activity. FSH, 8-bromo-cAMP, and TPA stimuli induced DNA binding complexes capable of binding to a TIMP-1 AP-1 site consensus sequence oligonucleotide. The AP-1 site binding complex(es) induced by all three treatments reacted with antibodies directed broadly against fos and jun protooncogene families and against the specific family members c-fos, junB, and junD but not c-jun proteins. Constitutive cAMP response element binding activity capable of binding an artificial cAMP response element binding site oligonucleotide was demonstrated in Sertoli cell nuclear extracts. This activity was minimally modulated by FSH, 8-bromo-cAMP, or TPA treatment. In summary, Sertoli cells secrete TIMP-1 and TIMP-2 that can be coordinately up-regulated by FSH through a cAMP, PKA-dependent pathway. A convergence of TPA, FSH, and cAMP mediated signals in prepubertal Sertoli cells may occur with the induction of specific AP-1 site binding complex(es) containing jun and fos proteins. Our data suggest that FSH stimulation of TIMP-2 expression may be regulated independently to that of TIMP-1. We propose that the ability of FSH to stimulate Sertoli cell TIMP activity suggests a central role for this hormone in the control of extracellular matrix turnover during testicular development at the level of metalloproteinase inhibition.

Original languageEnglish
Pages (from-to)2479-2487
Number of pages9
JournalEndocrinology
Volume135
Issue number6
Publication statusPublished - Dec 1994

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Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Sertoli Cells
Transcription Factor AP-1
Follicle Stimulating Hormone
Binding Sites
8-Bromo Cyclic Adenosine Monophosphate
Cyclic AMP-Dependent Protein Kinases
1-Methyl-3-isobutylxanthine
Aptitude
Response Elements
Protein Kinase Inhibitors
Oligonucleotides
Proto-Oncogene Proteins c-jun
Tissue Inhibitor of Metalloproteinases
Messenger RNA
Phosphodiesterase Inhibitors
Consensus Sequence
Metalloproteases
Dactinomycin

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Follicle-Stimulating Hormone Increases the Expression of Tissue Inhibitors of Metalloproteinases TIMP-1 and TIMP-2 and Induces TIMP-1 AP-1 Site Binding Complex(es) in Prepubertal Rat Sertoli Cells. / Ulisse, Salvatore; Farina, Antonietta R.; Piersanti, Deamaria; Tiberio, Antonella; Cappabianca, Lucia; D'Orazi, Gabriella; Jannini, Emmanuele A.; Malykh, Olga; Stetler-Stevenson, William G.; D'Armiento, Massimino; Gulino, Alberto; Mackay, Andrew R.

In: Endocrinology, Vol. 135, No. 6, 12.1994, p. 2479-2487.

Research output: Contribution to journalArticle

Ulisse, S, Farina, AR, Piersanti, D, Tiberio, A, Cappabianca, L, D'Orazi, G, Jannini, EA, Malykh, O, Stetler-Stevenson, WG, D'Armiento, M, Gulino, A & Mackay, AR 1994, 'Follicle-Stimulating Hormone Increases the Expression of Tissue Inhibitors of Metalloproteinases TIMP-1 and TIMP-2 and Induces TIMP-1 AP-1 Site Binding Complex(es) in Prepubertal Rat Sertoli Cells', Endocrinology, vol. 135, no. 6, pp. 2479-2487.
Ulisse, Salvatore ; Farina, Antonietta R. ; Piersanti, Deamaria ; Tiberio, Antonella ; Cappabianca, Lucia ; D'Orazi, Gabriella ; Jannini, Emmanuele A. ; Malykh, Olga ; Stetler-Stevenson, William G. ; D'Armiento, Massimino ; Gulino, Alberto ; Mackay, Andrew R. / Follicle-Stimulating Hormone Increases the Expression of Tissue Inhibitors of Metalloproteinases TIMP-1 and TIMP-2 and Induces TIMP-1 AP-1 Site Binding Complex(es) in Prepubertal Rat Sertoli Cells. In: Endocrinology. 1994 ; Vol. 135, No. 6. pp. 2479-2487.
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abstract = "Primary cultures of prepubertal rat Sertoli cells secrete two major tissue inhibitors of metalloproteinases: TIMP-1 (M, 28 K) and TIMP-2 (Mr 21 K). FSH stimulated Sertoli cell TIMP-1 and TIMP-2 activity in a time- and dose-dependent manner and also stimulated TIMP-1 and TIMP-2 protein and messenger RNA levels. These effects were mimicked by the cAMP analog, 8-bromo-cAMP, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. The protein kinase C activating phorbol ester phorbol myristrate acetate (TPA) stimulated TIMP-1 but not TIMP-2 activity and messenger RNA levels. Cycloheximide and actinomycin-D inhibited basal TIMP-1 and TIMP-2 activity and inhibited the ability of FSH, 8-bromo-cAMP, and TPA to stimulate TIMP activity. The protein kinase A (PKA) inhibitor AMP Rp isomer did not affect basal TIMP-1 and TIMP-2 activity or TPA-stimulated TIMP-1 activity. However, the PKA inhibitor markedly reduced FSH and 3-isobutyl-1-methylxanthine stimulation of TIMP-1 and TIMP-2 activity. FSH, 8-bromo-cAMP, and TPA stimuli induced DNA binding complexes capable of binding to a TIMP-1 AP-1 site consensus sequence oligonucleotide. The AP-1 site binding complex(es) induced by all three treatments reacted with antibodies directed broadly against fos and jun protooncogene families and against the specific family members c-fos, junB, and junD but not c-jun proteins. Constitutive cAMP response element binding activity capable of binding an artificial cAMP response element binding site oligonucleotide was demonstrated in Sertoli cell nuclear extracts. This activity was minimally modulated by FSH, 8-bromo-cAMP, or TPA treatment. In summary, Sertoli cells secrete TIMP-1 and TIMP-2 that can be coordinately up-regulated by FSH through a cAMP, PKA-dependent pathway. A convergence of TPA, FSH, and cAMP mediated signals in prepubertal Sertoli cells may occur with the induction of specific AP-1 site binding complex(es) containing jun and fos proteins. Our data suggest that FSH stimulation of TIMP-2 expression may be regulated independently to that of TIMP-1. We propose that the ability of FSH to stimulate Sertoli cell TIMP activity suggests a central role for this hormone in the control of extracellular matrix turnover during testicular development at the level of metalloproteinase inhibition.",
author = "Salvatore Ulisse and Farina, {Antonietta R.} and Deamaria Piersanti and Antonella Tiberio and Lucia Cappabianca and Gabriella D'Orazi and Jannini, {Emmanuele A.} and Olga Malykh and Stetler-Stevenson, {William G.} and Massimino D'Armiento and Alberto Gulino and Mackay, {Andrew R.}",
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T1 - Follicle-Stimulating Hormone Increases the Expression of Tissue Inhibitors of Metalloproteinases TIMP-1 and TIMP-2 and Induces TIMP-1 AP-1 Site Binding Complex(es) in Prepubertal Rat Sertoli Cells

AU - Ulisse, Salvatore

AU - Farina, Antonietta R.

AU - Piersanti, Deamaria

AU - Tiberio, Antonella

AU - Cappabianca, Lucia

AU - D'Orazi, Gabriella

AU - Jannini, Emmanuele A.

AU - Malykh, Olga

AU - Stetler-Stevenson, William G.

AU - D'Armiento, Massimino

AU - Gulino, Alberto

AU - Mackay, Andrew R.

PY - 1994/12

Y1 - 1994/12

N2 - Primary cultures of prepubertal rat Sertoli cells secrete two major tissue inhibitors of metalloproteinases: TIMP-1 (M, 28 K) and TIMP-2 (Mr 21 K). FSH stimulated Sertoli cell TIMP-1 and TIMP-2 activity in a time- and dose-dependent manner and also stimulated TIMP-1 and TIMP-2 protein and messenger RNA levels. These effects were mimicked by the cAMP analog, 8-bromo-cAMP, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. The protein kinase C activating phorbol ester phorbol myristrate acetate (TPA) stimulated TIMP-1 but not TIMP-2 activity and messenger RNA levels. Cycloheximide and actinomycin-D inhibited basal TIMP-1 and TIMP-2 activity and inhibited the ability of FSH, 8-bromo-cAMP, and TPA to stimulate TIMP activity. The protein kinase A (PKA) inhibitor AMP Rp isomer did not affect basal TIMP-1 and TIMP-2 activity or TPA-stimulated TIMP-1 activity. However, the PKA inhibitor markedly reduced FSH and 3-isobutyl-1-methylxanthine stimulation of TIMP-1 and TIMP-2 activity. FSH, 8-bromo-cAMP, and TPA stimuli induced DNA binding complexes capable of binding to a TIMP-1 AP-1 site consensus sequence oligonucleotide. The AP-1 site binding complex(es) induced by all three treatments reacted with antibodies directed broadly against fos and jun protooncogene families and against the specific family members c-fos, junB, and junD but not c-jun proteins. Constitutive cAMP response element binding activity capable of binding an artificial cAMP response element binding site oligonucleotide was demonstrated in Sertoli cell nuclear extracts. This activity was minimally modulated by FSH, 8-bromo-cAMP, or TPA treatment. In summary, Sertoli cells secrete TIMP-1 and TIMP-2 that can be coordinately up-regulated by FSH through a cAMP, PKA-dependent pathway. A convergence of TPA, FSH, and cAMP mediated signals in prepubertal Sertoli cells may occur with the induction of specific AP-1 site binding complex(es) containing jun and fos proteins. Our data suggest that FSH stimulation of TIMP-2 expression may be regulated independently to that of TIMP-1. We propose that the ability of FSH to stimulate Sertoli cell TIMP activity suggests a central role for this hormone in the control of extracellular matrix turnover during testicular development at the level of metalloproteinase inhibition.

AB - Primary cultures of prepubertal rat Sertoli cells secrete two major tissue inhibitors of metalloproteinases: TIMP-1 (M, 28 K) and TIMP-2 (Mr 21 K). FSH stimulated Sertoli cell TIMP-1 and TIMP-2 activity in a time- and dose-dependent manner and also stimulated TIMP-1 and TIMP-2 protein and messenger RNA levels. These effects were mimicked by the cAMP analog, 8-bromo-cAMP, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. The protein kinase C activating phorbol ester phorbol myristrate acetate (TPA) stimulated TIMP-1 but not TIMP-2 activity and messenger RNA levels. Cycloheximide and actinomycin-D inhibited basal TIMP-1 and TIMP-2 activity and inhibited the ability of FSH, 8-bromo-cAMP, and TPA to stimulate TIMP activity. The protein kinase A (PKA) inhibitor AMP Rp isomer did not affect basal TIMP-1 and TIMP-2 activity or TPA-stimulated TIMP-1 activity. However, the PKA inhibitor markedly reduced FSH and 3-isobutyl-1-methylxanthine stimulation of TIMP-1 and TIMP-2 activity. FSH, 8-bromo-cAMP, and TPA stimuli induced DNA binding complexes capable of binding to a TIMP-1 AP-1 site consensus sequence oligonucleotide. The AP-1 site binding complex(es) induced by all three treatments reacted with antibodies directed broadly against fos and jun protooncogene families and against the specific family members c-fos, junB, and junD but not c-jun proteins. Constitutive cAMP response element binding activity capable of binding an artificial cAMP response element binding site oligonucleotide was demonstrated in Sertoli cell nuclear extracts. This activity was minimally modulated by FSH, 8-bromo-cAMP, or TPA treatment. In summary, Sertoli cells secrete TIMP-1 and TIMP-2 that can be coordinately up-regulated by FSH through a cAMP, PKA-dependent pathway. A convergence of TPA, FSH, and cAMP mediated signals in prepubertal Sertoli cells may occur with the induction of specific AP-1 site binding complex(es) containing jun and fos proteins. Our data suggest that FSH stimulation of TIMP-2 expression may be regulated independently to that of TIMP-1. We propose that the ability of FSH to stimulate Sertoli cell TIMP activity suggests a central role for this hormone in the control of extracellular matrix turnover during testicular development at the level of metalloproteinase inhibition.

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