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Review
. 2017 Jun 28:8:430.
doi: 10.3389/fphys.2017.00430. eCollection 2017.

Insights into the Development of the Adult Leydig Cell Lineage from Stem Leydig Cells

Leping Ye  1 , Xiaoheng Li  1 , Linxi Li  1 , Haolin Chen  1 , Ren-Shan Ge  1
Affiliations
Review

Insights into the Development of the Adult Leydig Cell Lineage from Stem Leydig Cells

Leping Ye et al. Front Physiol. .

Abstract

Adult Leydig cells (ALCs) are the steroidogenic cells in the testes that produce testosterone. ALCs develop postnatally from a pool of stem cells, referred to as stem Leydig cells (SLCs). SLCs are spindle-shaped cells that lack steroidogenic cell markers, including luteinizing hormone (LH) receptor and 3β-hydroxysteroid dehydrogenase. The commitment of SLCs into the progenitor Leydig cells (PLCs), the first stage in the lineage, requires growth factors, including Dessert Hedgehog (DHH) and platelet-derived growth factor-AA. PLCs are still spindle-shaped, but become steroidogenic and produce mainly androsterone. The next transition in the lineage is from PLC to the immature Leydig cell (ILC). This transition requires LH, DHH, and androgen. ILCs are ovoid cells that are competent for producing a different form of androgen, androstanediol. The final stage in the developmental lineage is ALC. The transition to ALC involves the reduced expression of 5α-reductase 1, a step that is necessary to make the cells to produce testosterone as the final product. The transitions along the Leydig cell lineage are associated with the progressive down-regulation of the proliferative activity, and the up-regulation of steroidogenic capacity, with each step requiring unique regulatory signaling.

Keywords: Desert Hedgehog; Leydig cells; development; steroidogenic factor 1; testosterone.

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Figures

Figure 1
Figure 1
The scheme for the androgen production and possible involvement of Leydig cells in the life span. (A) Rat; (B) Human. SLC, FLC, PLC, ILC, ALC, and NLC represent stem, fetal, progenitor, immature, adult and neonatal Leydig cells, respectively. There are two androgen peaks for rats and three androgen peaks for human.
Figure 2
Figure 2
The difference of progenitor, immature and adult Leydig cells in the products of androgen in rats due to their differential expressions of steroidogenic enzymes. PLC, ILC, and ALC represent progenitor, immature, and adult Leydig cells, respectively. PLC lacks of 17β-hydroxysteroid dehydrogenase 3 (HSD17B3) but contains higher levels of 5α-reductase 1 (SRD5A1) and 3α-hydroxysteroid dehydrogenase (AKR1C9), thus producing primarily androsterone. ILC begins to express HSD17B3 and also contains SRD5A1 and AKR1C9, thus producing predominantly androstanediol. ALC secretes mainly testosterone due to the silence of SRD5A1. SRD5A1 is a unidirectional enzyme. Other steroidogenic enzymes are bidirectional.
Figure 3
Figure 3
The hormones and growth factors that may potentially regulate the development of Leydig cells. SLC, PLC, ILC, and ALC represent stem, progenitor, immature, and adult Leydig cells, respectively. ⊕, stimulation; θ, inhibition.
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