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Review
. 2016 Jul;28(7):10.1111/jne.12401.
doi: 10.1111/jne.12401.

Developmental and Functional Effects of Steroid Hormones on the Neuroendocrine Axis and Spinal Cord

L Zubeldia-Brenner  1 , C E Roselli  2 , S E Recabarren  3 , M C Gonzalez Deniselle  1   4 , H E Lara  5
Affiliations
Review

Developmental and Functional Effects of Steroid Hormones on the Neuroendocrine Axis and Spinal Cord

L Zubeldia-Brenner et al. J Neuroendocrinol. 2016 Jul.

Abstract

This review highlights the principal effects of steroid hormones at central and peripheral levels in the neuroendocrine axis. The data discussed highlight the principal role of oestrogens and testosterone in hormonal programming in relation to sexual orientation, reproductive and metabolic programming, and the neuroendocrine mechanism involved in the development of polycystic ovary syndrome phenotype. Moreover, consistent with the wide range of processes in which steroid hormones take part, we discuss the protective effects of progesterone on neurodegenerative disease and the signalling mechanism involved in the genesis of oestrogen-induced pituitary prolactinomas.

Keywords: androgens; hormonal programming; oestrogens; prolactin; steroid hormones.

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Conflict of interest statement

The authors of the manuscript have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Response of male fetal hypothalamic-pituitary-testis axis to vehicle (Control), androgen antagonist flutamide and androgen agonist dihydrotestosterone (DHT). Pregnant ewes received injections of vehicle, flutamide and DHT from gestation day (GD) 60 to 84 and fetuses were delivered on GD85 for evaluation. In control eugonadal male fetuses, LH secretion is tonically suppressed by androgens at this age to regulate normal testosterone (T) secretion driving normal androgen action which, in turn, masculinizes the ovine sexually dimorphic nucleus (oSDN). Exposure to flutamide blocks negative feedback resulting in elevated LH concentrations, enlarged testis & increased testicular T secretion. The increased T competes with the competitive antagonist flutamide for the androgen receptor and leads to partial, instead of full, inhibition of oSDN masculinization. Exogenous DHT exposure enhances negative feedback further suppressing LH secretion leading to smaller testis and reduced levels of testicular T. The result of DHT treatment is reduced exposure of the developing SDN to endogenous T and incomplete masculinization. Both results are consistent with a role for androgen receptor activation in the masculinization of the ovine SDN.
Figure 2
Figure 2
A: Digital images of paraffin sections of the ventral horn from cervical spinal cord stained with cresyl violet. Images show motoneurons with normal appearance (upper left), two intensely vacuolated cells (arrows) in an untreated Wobbler mouse (middle graph), and 4 motoneurons with normal appearance and 1 vacuolated motoneuron (arrow) in a progesterone treated Wobbler (upper right) Magnification: 600X. Lower graphs show electron microscopy of mitochondria from a motoneuron of a control mouse (lower left), an untreated Wobbler mouse (middle) and a Wobbler mouse receiving progesterone (PROG) (lower right). Motoneurons from Wobblers show massive vacuolation disrupting the outer, inner mitochondrial membranes and cristae (lower middle graph, asterisk). Motoneurons from PROG treated Wobblers show some mitochondria with a better conservation of the membrane system, including the cristae. Magnification: 50,000X. B: Activity of the mitochondrial respiratory enzyme complex I in the cervical region of the spinal cord of Wobbler mice and Wobbler mice receiving progesterone treatment. Progesterone increased complex I activity in cervical spinal cord from Wobblers (*** p<0.001 vs. Wobbler). Results were expressed as % of complex I activity of control. C: Content of nNOS and MnSOD in mitochondrial fractions from the cervical cord of Wobbler mice and Wobbler receiving PROG. Wobbler vacuolated mitochondria showed high expression of mitochondrial nNOS (nNOSmt) and low activity and expression of manganese superoxide dismutase (MnSOD). Progesterone treatment in Wobblers significantly modified the high nNOSmt and the low MnSOD contents in mitochondria.
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