Skip to Content
Merck
  • IGSF1 Does Not Regulate Spermatogenesis or Modify FSH Synthesis in Response to Inhibins or Activins.

IGSF1 Does Not Regulate Spermatogenesis or Modify FSH Synthesis in Response to Inhibins or Activins.

Journal of the Endocrine Society (2021-04-03)
Emilie Brûlé, Charlotte A Heinen, Courtney L Smith, Gauthier Schang, Yining Li, Xiang Zhou, Ying Wang, Sjoerd D Joustra, Jan M Wit, Eric Fliers, Sjoerd Repping, A S Paul van Trotsenburg, Daniel J Bernard
ABSTRACT

Loss-of-function mutations in the X-linked immunoglobulin superfamily, member 1 (IGSF1) gene result in central hypothyroidism, often associated with macroorchidism. Testicular enlargement in these patients might be caused by increases in follicle-stimulating hormone (FSH) levels, as IGSF1 has been proposed to function as an inhibin B receptor or as an inhibitor of activin type I receptor (ALK4) activity in pituitary gonadotrope cells. If true, loss of IGSF1 should lead to reduced inhibin B action or disinhibition of activin signaling, thereby increasing FSH synthesis. Here, we show that FSH levels and sperm counts are normal in male Igsf1 knockout mice, although testis size is mildly increased. Sperm parameters are also normal in men with IGSF1 deficiency, although their FSH levels may trend higher and their testes are enlarged. Inhibin B retains the ability to suppress FSH synthesis in pituitaries of Igsf1-knockout mice and IGSF1 does not interact with ALK4 or alter activin A/ALK4 stimulation of FSHβ (Fshb/FSHB) subunit transcription or expression. In light of these results, it is unlikely that macroorchidism in IGSF1 deficiency derives from alterations in spermatogenesis or inhibin/activin regulation of FSH.

MATERIALS
Product Number
Brand
Product Description

Millipore
MILLIPLEX® Mouse Pituitary Magnetic Bead Panel - Endocrine Multiplex Assay, The analytes available for this multiplex kit are: ACTH, BDNF, FSH, GH, Prolactin, TSH, LH.
Sigma-Aldrich
Bovine Serum Albumin, lyophilized powder, 1× crystallized, ≥97% (agarose gel electrophoresis)
Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-15, ascites fluid
Sigma-Aldrich
Medium 199, With Hanks′ salts and sodium bicarbonate, without L-glutamine, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Monoclonal Anti-c-Myc antibody produced in mouse, clone 9E10, ascites fluid
Sigma-Aldrich
Monoclonal Anti-HA antibody produced in mouse, clone HA-7, ascites fluid