Faculty Opinions recommendation of Hormonal stimulation of spermatogenesis: a new way to treat the infertile male with non-obstructive azoospermia?

Stimulation of gonadal cells by lutropins such as human chorionic gonadotropin (hCG) is often transient and followed by down-regulation and/or desensitization of lutropin receptors (LHR). Here we describe desensitization/resensitization of LHR in Y-1 adrenal cell lines (termed Y-1L) expressing a rat cDNA lacking most 5' and 3' LHR untranslated regions under the control of a metallothionein promoter. Using a simple morphological assay in which stimulated cells are round and unstimulated cells are flat, we identified clones that rounded and remained round and others that became insensitive to lutropin stimulation and reverted to their flat appearance within 2-4 h. Flattened cells were insensitive to further hormonal stimulation but rounded after treatments with cholera toxin, forskolin, or cyclic AMP, showing that loss of responsiveness was associated with an early step in signal transduction, not loss of rounding potential. Removing the lutropin stimulus for at least 90-120 min reversed hormone insensitivity, even in the presence of the protein synthesis inhibitor puromycin. The number of surface bound receptors did not change during a cycle of rounding/flattening and hCG bound to rounded or flattened cells was replaced equally by radioiodinated hCG during incubations at 4 degrees C. Thus, desensitization/resensitization of LHR in Y-1L cells occurred in the absence of new receptor synthesis, receptor degradation, or receptor recycling. These observations suggest that LHR desensitization/resensitization in Y-1L cells was closely coupled to receptor occupancy and that this cell line may be useful for identifying factors that modulate the activities of occupied receptors.

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Mechanisms of genotoxic effects of hormones

Genetika ◽

10.2298/gensr0203059d ◽

2002 ◽

Vol 34 (2-3) ◽

pp. 59-71

Author(s):

Ninoslav Djelic

Keyword(s):

Oxidative Stress ◽

Biological Evolution ◽

Genotoxic Effects ◽

Hormonal Stimulation ◽

Sexual Steroids ◽

Group Data ◽

Cell Components ◽

Phenolic Group ◽

Endogenous Substances ◽

Stimulation Of

A concept that compounds commonly present in biological systems lack genotoxic and mutagenic activities is generally in use, hence a low number of endogenous substances have ever been tested to mutagenicity. Epidemiological and experimental analyses indicated, however, that sexual steroids could contribute to initiation and/or continuation of malign diseases. Detailed studies using methods of biochemistry, molecular biology, cytogenetics and other branches, showed that not only epigenetic mechanisms, such as a stimulation of cell proliferation, but also certain hormones, that can express genotoxic effects, such as covalent DNA modification, then chromosomal lesions and chromosomal aberrations, are in the background of malign transformation under activities of hormones. In the case of oestrogens, it was shown that excessive hormonal stimulation led to a metabolic conversion of these hormones to reactive intermediates with formation of reactive oxygenic derivates, so that cells were virtually under conditions of oxidative stress. Individual and tissue susceptibility to occurrence of deterioration of DNA and other cell components generally results from the differences in efficiency of enzymic and non-enzymic mechanisms of resistance against oxidative stress. Besides, steroid thyeroid hormones and catecholamine (dopamine, noradrenaline/norepinephrine and adrenaline) can express genotoxic effects in some test-systems. It is interesting that all above mentioned hormones have a phenolic group. Data on possible genotoxic effects of peptide and protein hormones are very scarce, but based on the available literature it is considered that this group of hormones probably lacks mutagenic activities. The possibility that hormones, as endogenous substances, express mutagenic activities results from the fact that DNA is, regardless of chemical and metabolic stability susceptible, to a certain extent, to changeability compatible with the processes of the biological evolution.

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SGK phosphorylates Cdc25 and Myt1 to trigger cyclin B–Cdk1 activation at the meiotic G2/M transition

The Journal of Cell Biology ◽

10.1083/jcb.201812122 ◽

2019 ◽

Vol 218 (11) ◽

pp. 3597-3611 ◽

Cited By ~ 7

Author(s):

Daisaku Hiraoka ◽

Enako Hosoda ◽

Kazuyoshi Chiba ◽

Takeo Kishimoto

Keyword(s):

Somatic Cell ◽

Cyclin A ◽

Pi3k Pathway ◽

Cyclin B ◽

Hormonal Stimulation ◽

Oocyte Meiosis ◽

M Phase ◽

Mitosis And Meiosis ◽

Cell Mitosis ◽

Stimulation Of

The kinase cyclin B–Cdk1 complex is a master regulator of M-phase in both mitosis and meiosis. At the G2/M transition, cyclin B–Cdk1 activation is initiated by a trigger that reverses the balance of activities between Cdc25 and Wee1/Myt1 and is further accelerated by autoregulatory loops. In somatic cell mitosis, this trigger was recently proposed to be the cyclin A–Cdk1/Plk1 axis. However, in the oocyte meiotic G2/M transition, in which hormonal stimuli induce cyclin B–Cdk1 activation, cyclin A–Cdk1 is nonessential and hence the trigger remains elusive. Here, we show that SGK directly phosphorylates Cdc25 and Myt1 to trigger cyclin B–Cdk1 activation in starfish oocytes. Upon hormonal stimulation of the meiotic G2/M transition, SGK is activated by cooperation between the Gβγ-PI3K pathway and an unidentified pathway downstream of Gβγ, called the atypical Gβγ pathway. These findings identify the trigger in oocyte meiosis and provide insights into the role and activation of SGK.

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